Epigenetic Control of Development, Homeostasis and Reproduction
CNC...@aol.com
I.
Control Systems in Metazoans
Any open system tends to lose its structural order and so do
living systems. But living systems could not have evolved without
evolving the capability for maintaining, within certain limits,
their characteristic structural order, underlying their vital
functions (growth, reproduction, evolution, etc).
Living systems, as highly improbable structures, are more
liable to entropic influences and are in every moment losing
their structural order at both the sub- and supracellular
level. At the molecular level, the genome performs a
great deal of work for maintaining a constant the
internal cell environment but epigenetic mechanisms
are also involved in the regulation of the specific
arrangement of supramolecular structures within the cell.
Metazoans, and unicellulars in general, are faced with an
aditional tasks: they have to coordinate the function of the
myriad of cells in order to perform new supracellular,
systemic functions. The function of every cell is
subordinated to the function of the organism. The individual
cell in multicellulars is not as free as a unicellular is;
extracellular constraints have limited its freedom. The freedom
of the individual cells in metazoans has to be sacrificed for
the sake of the freedom of the multicellular organism. But
the function of the multicellular organism requires that it
is capable of maintaining its unavoidably degrading structure
at the cellular and supracellular level. Easy as it is to say,
this control of the the activity of individual cells was a
formidable challenge to evolution of multicellular life.
In order to function, even a simple device as a thermostat
needs a control mechanism that would be able to sense the
level of temperature and switch off/on a heat-producing
device for maintaining the internal temperature within limits
determined by a set point. If a control system is necessary
for the function of a very simple device such as a thermostat,
the functioning and the very existence of an incomparably
more complex system, such as an unicellular
or multicellular organism is unimaginable without
a control system.
The control system would be capable of continually
monitoring the state of the structure of the system at the
cell level, to compare it with the normal structure, to
determine deviations from the norm and send
instructions for restoring the normal structure. Such a
control system that would control the structure and
coordinate activities of the myriad of cells in the system
could not reside in a single cell (no cell could monitor
the status of the structure troughout the animal body
or send signals or restoring the normal state
throughout the body) but in a supracellular structure.
Tracing back the evolution of metazoan life in very simple
organisms of the type of cnidarians we see that this
control is function of their diffuse nervous system,
which has access to every part of the animal structure.
Due to its pervasive presence throughout the cnidarian body,
the capability of neural cells to receive, process, integrate
and transmit the information on external and internal
environment to other cells throughout the animal body,
the primitive nervous system of cnidarians was the only
system aparently meeting all the basic requirements of a
control system for maintaining the structure and functions
in these organisms. Indeed, the nervous system in these
simple animals controls all the vital functions.
The network of neurons in this diffuse nervous system
is specialized in receiving stimuli from external and internal
environment, in integrating them and sending
electrical/chemical signals throughout the body for coordinating
activities of different types of cells in cnidarians.Ultimately,
all the behavioral, reproductive and growth phenomena,
including metamorphosis, in Cnidaria are under neural
control via neurohormones released by secretory neurons
(Hartenstein, V. 2006. The neuroendocrine system in
inveretbrates: a developmental and evolutionary
perspective. Endocrinology 190: 555-570).
It may be not be purely by chance that the Cambrian
explosion coincided with the evolution of the neuron and
the nervous system. It may also not be a game of chance
the fact that sponges that have a comparable degree of
structural complexity (a comparable number
of differentiated cells) with cnidarians but evolved no
nervous system remained a "dead end" of evolution.
"The origin of differentiated nervous tissue must have
proceeded in a number of steps, of which the first
would obviously be the development of a specialized
receptor monitoring changes in the extrernal environment,
such as light. In order for the detected changes to influence
the organism, the receptor or primitive neuron would have
to communicate in some way with the rest of the organism....
That scenario defines a minimal endocrine structure,
in which a receptor becomes also an independent effector,
secreting a molecule that carries a message to all parts
of the organism." (Gorbman, A. and Davey, K.1991.
Endocrines. In: Neural and Integrative Animal Physiology
4th ed. C.L. Prosser ed., Wiley-Liss, p.744).
While capable of regulating processes of growth and
reproduction in simplest invertebrates like cnidarians, the
simple diffuse nervous system (in Hydra consisting of just
6700 neurons) obviously was not capable of controlling
and regulating these processes in more complex invertebrates
and vertebrates. This led to evolution of concentration of
neurons in structures like ganglia and more generally
centralization of he nervous system in cerebral structures.
This was associated with specialization of hormone-secreting
glands, which ultimately were under neural control,
in a process that led to what we know as neurohormonal
system.
In higher invertebrates, such as crustaceans and insects,
the processes of reproduction and growth, including
processes of metamorphosis and apoptosis, are
under hormonal control of specialized endocrine glands,
creating the impression that the endocrine system in
these invertebrate classes took the control of growth,
metamorphosis and reproduction. This impression, as
we know, is false: secretion of these hormones
(ecdysone and juvenile in insects, e.g.) is under strict
neural control, in the meaning that their production
and secretion is induced by brain chemical signals
(brain neuropeptides).
The further`process of centralization of the nervous
system in vertebrates was associated with addition
of another level in the hierarchy of neuro-hormonal
control of vital processes of growth and reproduction
and even evolution (remember numerous cases of
evolutionary changes that involved only changes in the
timing and amount of secretion/suppression of hormones).
How do tese these glands know when and how much of
each hormone have to secrete in order to regulate
growth, development and reproduction of animals?
Where the pertinent information comes from?
rnorman
As a neurophysiologist, I certainly won't deny the importance of
nervous systems. However I am under the impression (delusion,
perhaps?) that plants also have highly evolved, complexly coordinated
bodies that evolved completely without nervous systems.
Nervous systems are useful in motile, active organisms. Nervous
systems are not the key to understanding evolution and development.
VoiceOfReason
CNCa...@aol.com wrote:
> Epigenetic Control of Development, Homeostasis and Reproduction
>
> I.
>
> Control Systems in Metazoans
>
> Any open system tends to lose its structural order and so do
> living systems.
Living systems tend to lose structural order? Examples?
> But living systems could not have evolved without
> evolving the capability for maintaining, within certain limits,
> their characteristic structural order, underlying their vital
> functions (growth, reproduction, evolution, etc).
That's a relief.
> Living systems, as highly improbable structures,
I'm improbable? That's disconcerting...
> are more
> liable to entropic influences and are in every moment losing
> their structural order at both the sub- and supracellular
> level. At the molecular level, the genome performs a
> great deal of work for maintaining a constant the
> internal cell environment but epigenetic mechanisms
> are also involved in the regulation of the specific
> arrangement of supramolecular structures within the cell.
Ah, so it's the genome that's keeping me up at night. Damn
construction workers...
<...>
Steven L.
> As a neurophysiologist, I certainly won't deny the importance of
> nervous systems. However I am under the impression (delusion,
> perhaps?) that plants also have highly evolved, complexly coordinated
> bodies that evolved completely without nervous systems.
Not if you broaden your definition of "nervous system" just a bit.
The way a Venus FlyTrap traps insects, is that when an unfortunate
insect stimulates the hairs of the trap, an electrochemical impulse is
propagated which stimulates the cells of the trap's walls to close on
the insect. That's not all that different from a reflex neural response
in an animal, is it?
Maybe this is a kind of convergent evolution: To be capable of
relatively high speed movements, plants had to evolve the ability to
respond to electrochemical impulses, just as the nervous systems of
animals do.
--
Steven L.
Email: sdli...@earthlinkNOSPAM.net
Remove the NOSPAM before replying to me.
rnorman
There are cellular activities in plants that mirror those in neurons:
the algae Chara and Nitella also make action potentials, as does the
sensitive plant Mimosa pudica. Plants also have well developed
hormonal control systems. That is not what cabej is getting at in his
"neuronal information" notions of metazoan development and evolution.
The problem, as he puts it, is that multicellular organisms: "have to
coordinate the function of the myriad of cells in order to perform
new supracellular, systemic functions." He argues that: a "control
system that would control the structure and coordinate activities of
the myriad of cells in the system could not reside in a single cell
(no cell could monitor the status of the structure troughout the
animal body or send signals or restoring the normal state throughout
the body) but in a supracellular structure." Hence he argues that the
animal nervous system is the only system capable of doing such a thing
and that somehow this neuronal information is separate and distinct
from genetic information, yet is passed down from generation to
generation and so is a neglected mechanism of epigenetic evolution.
CNC...@aol.com
There is no question that plants are not simple organisms (although
incomparably simpler than you and I, e.g.). But if you pay a
little more attention you are going to see that all I am suggesting
is that what a multicellular organism needs to maintain its normal
structure is a control system, not necessarily a "nervous system".
In this post, as shown by the title, I choose to write about the
control system of metazoans, the nervous system, which is known
best.
> Nervous systems are useful in motile, active organisms. Nervous
> systems are not the key to understanding evolution and development.- Hide quoted text -
>
We all know that the nervous system is necessary for the
movement of animals; it determines our behavior, our thoughts
and ideas. However, a closer look at the individual development
of a bird, a reptile or a mammal, like us, from zygote to adulthood,
shows that
1. Signal cascades for the development of numerous animal organs
start in the CNS. No other organ or organ system but the central
nervous
system is observed to "engender a network of inductions that give rise
to
the different cells, tissues and organs of embryos and adults"
(Hall, B.K. 1998. Evolutionary Developmental Biology. Second edition.
p.134).
2. The nervous system is the first organ system that develops
and is operational in all these embryos, although these embryous
do not need to move or think while still in the womb (the common
sense would suggest that blood circulation and excretory system
would be first to develop).
3. The evidence that signal cascades for evolutionary changes
start in the CNS.
4. All the known signal for transgenerational plasticity come from
the central nervous system.
5. Numerous cases of the developmental plasticity where from eggs
of the same brood, i.e. of the same genotype, and reared in the same
environment, offspring with discrete different morphologies are
produced in particular proportions. Signal cascades for these
epigenetic changes in morphology come from the central nervous system
Does not all this suggests to you a possible key role of the nervous
system in individual development and evolution?
N.C.
CNC...@aol.com
> CNCa...@aol.com wrote:
> > Epigenetic Control of Development, Homeostasis and Reproduction
>
> > I.
>
> > Control Systems in Metazoans
>
> > Any open system tends to lose its structural order and so do
> > living systems.
>
> Living systems tend to lose structural order? Examples?
Millions of cells we are unavoidably losing any moment.
> > But living systems could not have evolved without
> > evolving the capability for maintaining, within certain limits,
> > their characteristic structural order, underlying their vital
> > functions (growth, reproduction, evolution, etc).
>
> That's a relief.
>
> > Living systems, as highly improbable structures,
>
> I'm improbable? That's disconcerting...
Do not worry. It is only from a thermodynamic point of view.
N.C.
rnorman
I believe you are seriously mistaken about the role of the nervous
system in development. For example, the BK Hall quotation you cite
really says that gastrulation is what initiates a pattern of
induction, not specifically the nervous system whose induction begins
during gastrulation. The nervous system does develop early, but is
most definitely NOT operational during early development, that is,
during the early stages of morphogenesis and embryogenesis. Yes,
there are most definitely inductive interactions between developing
neural tissues and adjacent tissues, but there are also most
definitely inductive interactions between neighboring epithelial or
mesothelial tissues without nervous involvement. There are elaborate
cellular signaling mechanisms that are part of the repertoire of the
nervous system. But they are also part of the repertoire of pretty
much all animal cells.
So, on item 1 above, I believe you have misinterpreted your citation.
On item 2 above, the circulatory system develops and is functional
before the CNS is well formed, certainly before it is truly
functional.
On items 3, 4, and 5 above, you present no evidence but simply make
rather sweeping statements.
The "organizational information" and the "regulatory signaling"
features needed (and I most definitely admit that these both are
needed) derive from the expression of the genome to produce known and
as yet undetermined inter- and intra-cellular signals that influence
both the differential growth and movement of cells, hence
morphogenesis, and further expression of the genome, hence
differentiation. Nervous tissue plays a role in this process, as do
all tissues, but does not play a "central organizing" or
"informational center" role in it.
MISAHA
control system" that dares to talk about the latter beyond the
biochemical level. Congratulations!
In our book "LIFE and MIND - in Search of the Physical Basis" 2007,
(see: www.misaha.com) I postulate the structure and the function of
the biofield epigenetic control system of the organism. Yes, heretic
neo-vitalism but it must be revitalized.
Postulated Definition
The epigenetic Biofield Control System (BCS) is the operative control
system of the organism. In BCS, the genetic information is re-encoded
on some other than biochemical physical carrier. It evolves in
ontogenesis into a hierarchy of subordinate BCS of the whole organism,
organs, tissues and cells. At all levels it holds four fundamental
programs of life: development, maintenance, reproduction, and death.
The mind is an essential part of the BCS at the whole organism level,
serving behavioral aspects of all fundamental programs (in addition to
the physiological aspect—see Fig.1)
Figure 1
Control System of the Organism
(control subsystems exist only in higher biological taxa)
rnorman
You have a truly important, possibly revolutionary approach. That is,
of course, provided that you can produce a credible physical mechanism
to implement this control system and provide some actual evidence that
your mechanism is, indeed, at work. Of course, you can satisfy these
two simple requests, can't you?
MISAHA
> of course, provided that you can produce a credible physical mechanism
> to implement this control system and provide some actual evidence that
> your mechanism is, indeed, at work. Of course, you can satisfy these
> two simple requests, can't you?
To discover phisical forces manifested in life is the upcoming task of
physics. They seem to have properties of energy and information
(broader than Shenon's). Some of the approaches are presented in four
experimental articles in our book.
Perplexed in Peoria
We all know that the nervous system is necessary for the
movement of animals; it determines our behavior, our thoughts
and ideas. However, a closer look at the individual development
of a bird, a reptile or a mammal, like us, from zygote to adulthood,
shows that
1. Signal cascades for the development of numerous animal organs
start in the CNS. No other organ or organ system but the central
nervous system is observed to "engender a network of inductions that give rise
to the different cells, tissues and organs of embryos and adults"
(Hall, B.K. 1998. Evolutionary Developmental Biology. Second edition.
p.134).
2. The nervous system is the first organ system that develops
and is operational in all these embryos, although these embryous
do not need to move or think while still in the womb (the common
sense would suggest that blood circulation and excretory system
would be first to develop).
-----------------------
PiP: Whose common sense? Not the common sense of anyone who
has previously puzzled over the 'paradox' of male nipples.
-----------------------
3. The evidence that signal cascades for evolutionary changes
start in the CNS.
--------------------------------
PiP: I'm pretty sure you meant to say "signal cascades for
developmental changes". However, if you did mean to
suggest that the CNS is the starting point for the signal
cascades which direct evolution, then you are even crazier
than we realized.
----------------------------------
4. All the known signal for transgenerational plasticity come from
the central nervous system.
----------------------------------
PiP: This one puzzles me. The signal's come from whose
CNS? The parent's? How does this work in birds and
reptiles, to say nothing of insects? Or does the signal
come from the CNS of the embryo? And if so, doesn't
this contradict #3 above? Because the CNS of the embryo
cannot then be the starting point of the causal signal cascade.
Because it needed some signal from the parent.
------------------------------
5. Numerous cases of the developmental plasticity where from eggs
of the same brood, i.e. of the same genotype, and reared in the same
environment, offspring with discrete different morphologies are
produced in particular proportions. Signal cascades for these
epigenetic changes in morphology come from the central nervous system
-------------------------------
PiP: Huh??? Eggs from the same brood have the same genotype?
Mind letting us know what species you are talking about? It
sure ain't standard Mendelian, and it ain't haplo-diploid, but maybe
there is a beastie for which it is true.
----------------------------------
Does not all this suggests to you a possible key role of the nervous
system in individual development and evolution?
-----------------------
PiP: It kinda suggests there was a problem in your case. ;-)
John Harshman
> -------------------------------
> PiP: Huh??? Eggs from the same brood have the same genotype?
> Mind letting us know what species you are talking about? It
> sure ain't standard Mendelian, and it ain't haplo-diploid, but maybe
> there is a beastie for which it is true.
> ----------------------------------
Peripheral point: There are species of insects (and perhaps other taxa
for all I know) in which one-celled zygotes divide many times to produce
many one-celled zygotes before any of them develops into an embryo, thus
producing dozens or hundreds of genetically identical individuals
(ignoring the various mutations during replication). Happens a lot in
fig wasps, if I recall.
Garamond Lethe
> On Jan 30, 1:11 pm, VoiceOfReason <papa_fo...@hotmail.com> wrote:
>> CNCa...@aol.com wrote:
>> > Epigenetic Control of Development, Homeostasis and Reproduction
>>
>> > I.
>>
>> > Control Systems in Metazoans
>>
>> > Any open system tends to lose its structural order and so do living
>> > systems.
>> Living systems tend to lose structural order? Examples?
>
> Millions of cells we are unavoidably losing any moment.
This is why babies evaporate minutes after they're born.
<snip>
Kent Paul Dolan
of evolution":
>>>> Any open system tends to lose its structural
>>>> order and so do living systems.
>>> Living systems tend to lose structural order?
>>> Examples?
>> Millions of cells we are unavoidably losing any
>> moment.
> This is why babies evaporate minutes after they're
> born.
xanthian.
Out of the uterus into the plasma field.
CNC...@aol.com
First, let me present the full Hall's sentence:
"Induction of the central nervous system begins during gastrulation,
initiating a network of inductions that give rise
to the different cells, tissues and organs of embryos and adults."
(Hall, B.K. 1998. Evolutionary Developmental Biology. Second edition.
p.134).
I believe that Hall makes it clear that it is the central nervous
system that initiates
"a network of inductions" not the gastrulation which is not a
structure
but a stage of development. If you are somehow familiar with his work
you
should know that he believes in the central control of developmental
processes.
Second, as a neurobiologist you know that formation of the central
nervous system follows gastrulation with a little overlapping.
http://scienceblogs.com/pharyngula/2007/05/basics_the_pharyngula_stage.php
>The nervous system does develop early, but is
> most definitely NOT operational during early development, that is,
> during the early stages of morphogenesis and embryogenesis.
You certainly admit that the central nervous system is the first organ
system that develops and that neurons differentiate even in the neural
tube
but it is difficult for you to admit that the central nervous system
is the source of the signals for development of different organs.
I am going to present some examples to show you that this takes place
indeed.
>Yes, there are most definitely inductive interactions between developing
> neural tissues and adjacent tissues, but there are also most
> definitely inductive interactions between neighboring epithelial or
> mesothelial tissues without nervous involvement. There are elaborate
> cellular signaling mechanisms that are part of the repertoire of the
> nervous system. But they are also part of the repertoire of pretty
> much all animal cells.
I am avoiding long and useless discussions on irrelevant interactions.
I will simply present a few of numerous examples of signals from
the brain that induce development of organs.
1. Pulses of ecdysone biosynthesis "direct the destruction of obsolete
larval tissues and their replacement by tissues and structures that
form the adult fly...via the precise stage- and tissue-specific
regulation
of key death effector genes. (Draizen et al., 1999). And, as it is
known,
these pulses ate just echo of pulses of the neuropeptide PTTH
(prothoracicotropic hormone) released by the brain.
2. Metamorphosis in molluscs, in cnidarians, in insects and in
amphibians.
3. Control of muscle fiber differentiation durin myogenesis in
Drosophila
(Fernandes and Keshishian, 2005)Based on experimental evidence, it is
concluded that the motoneuron influences both the number of cells
available for fusion, as well as potentially regulates the fusion
events themselves. This in our view is an elegant mechanism for
controlling muscle fiber differentiation during myogenesis, and may
have evolved as a way to ensure that muscle primordia develop into
muscles that meet the diverse demands placed on them by the nervous
system. (Fernandes and Keshishian, 2005)
4. After formation of the neural tube and the CNS, the heart is the
first
embryonic organ to develop in most vertebrates studied. The neural
tube
sends signals (Wnt3 and Wnt8) that inhibit induction of
cardiogenesis
and promote blood cell differentiation of mesoderm cells along the
whole
of its length, except for the region where the heart nomally develops.
By simply using Wnt antagonists it has been possible to induce
ectopic
heart development (Schneider and Mercola, 2001; Tzahor and Lassar,
2001).
5. In the embryonic limb skin VEGFs secreted by local nerves induce
formation of
blood vessels, thus explaining the old anatomic observation on the
association of
nerves and blood vessels:
"Peripheral nerves provide a template that determines the organotypic
pattern of blood vessel branching and arterial differentiation in the
skin, via local secretion of VEGF." (Mukoyama et al., 2002).
For numerous examples of the neural control of development of organs
and organ
systems visit my website
nelsoncabej.com or http://www.epigeneticscomesofage.com
> So, on item 1 above, I believe you have misinterpreted your citation.
Please, see above, who has misinterpreted and the examples I present
on
the neural control of organogenesis here and in my website.
> On item 2 above, the circulatory system develops and is functional
> before the CNS is well formed, certainly before it is truly
> functional.
The example 5 shows the contrary:
"Peripheral nerves provide a template that determines the organotypic
pattern of blood vessel branching and arterial differentiation in the
skin, via local secretion of VEGF. (Mukoyama et al., 2002) (certainly,
honest mistake).
> On items 3, 4, and 5 above, you present no evidence but simply make
> rather sweeping statements.
In relation to 3, I have already presented examples of the evolution
of
the change in the size of M. sexta, evolution of caste polymorphism in
ants,
loss of teeth in birds, but you can further read on the role of
auditory mechanisms,
olfactory mechanisms, visual mechanisms, and electrosensory mechanisms
in
sympatric speciation in chapter 20 of my book Epigenetic Principles of
Evolution
or in my website
In relation to 4 (role of the nervous system in transgenerational
plasticity) look at the following example:
Under normal to favorable conditions in environment, Daphnia magna
reproduces
asexually by producing only diploid female offspring. It responds to
the stressful environemntal conditions (shortening of the photoperiod,
drop in food quality and quantity, crowding etc.) by activating the
neuroendocrine cascade CHH (crustacean
hyperglycemic neuropeptides --> hormone methyl farnesoate via the CNS
-->
X organ/sinus gland complex --> ovary. Thus the crustacean transduces
the
unfavorable environmental stimuli into inherited phenotypic changes in
the offspring,
giving birth to both male and sexualy responsive female individuals,
leading to sexual reproduction and production of eggs that are
different from the parental eggs in
morphology (contain a protective cover ephippium), biochemistry
(contain substances
that protect them from drying and freezing), and in the life history
(can delay hatching for many yearsuntil favorable conditions in the
environment return) (Rider et al. 2005).
I hope to have been helpful.
N.C.
Perplexed in Peoria
Cool. I figured it was possible, but didn't know of any examples.
And for all I know, this may be the 'broods' that Mr. Cabej was
referring to.
Perplexed in Peoria
Desertphile
<xant...@well.com> wrote:
> File under: "need for diapers vanishes with progress
> of evolution":
> >>>> Any open system tends to lose its structural
> >>>> order and so do living systems.
>
> >>> Living systems tend to lose structural order?
> >>> Examples?
>
> >> Millions of cells we are unavoidably losing any
> >> moment.
>
> > This is why babies evaporate minutes after they're
> > born.
ROTFL! Oh, so that's what happened to my first born. We just
thought he wandered off somwhere and the dingos got 'em.
--
http://desertphile.org
Desertphile's Desert Soliloquy. WARNING: view with plenty of water
"Why aren't resurrections from the dead noteworthy?" -- Jim Rutz
Earle Jones
<891e7b15-848a-4ac8...@x6g2000pre.googlegroups.com>,
MISAHA <mis...@aol.com> wrote:
*
In other words, you first:
Make an interesting hypothesis.
Then, it is the job of physics to find the data to support it.
Isn't that a bit ass-backwards?
earle
*
Perplexed in Peoria
Make an interesting hypothesis.
-----------------
PiP:
Yes, according to Popper, that is ass-backwards. It is the job
of physics to find data to *refute* it.
But more importantly, we here at talk origins need to celebrate
the fact that '[t]his is the only group referred to by Google Alert
for "Epigenetic control system" that dares to talk about the latter
beyond the biochemical level.' And to thank Mr Cabej for
winning us that distinction.
CNC...@aol.com
II. Neural Control of Homeostasis
As pointed out in the first post of this series, the problems with
metazoan life do not end with erection of their structure. In order
to be able to reproduce themselves adult metazoans have to be
able to maintain their thermodynamicaly unstable structure, i.e.
to resist and conquer the thermodynamic forces of destruction.
The maintenance of a stable internal environment, Claude
Bernard's "fixete du milieu interieur" and Walter Cannon's
"homeostasis", is considered here in a broader meaning, to
include maintenance of the whole animal structure at both cellular
and supracellular, organismic level.
Easy as it is to say, the maintenance of the enormously complex
metazoan structure requires a correspondingly complex control
system that would be capable to continually monitor the structure
and send the pertinent information to the control center. The control
center has to process that information and by comparing it with
the normal structure make decisions and send instructions (chemical
messages) for restoring the normal structure.
The central nervous system is the biological structure that meets all
the requirments of a control system with the receptor (sensory)
apparatus for monitoring the metazoan structure at the cell level,
with
the controller (the central nervous system) for processing the
afferent
information and starting signal cascades (algorithms) for restoring
the
normal structure. Any attempt for explaining this from a genetic
point
view has not succeeded to go beyond obfuscate impenetrable
phraseology.
I am going to try here to explain in concrete, as opposed to
theoretical,
terms the epigenetic nature of the control system for the maintenance
of the homeostasis of the adult animal phenotype, the animal
structure
and function. Normal animal physiology as a whole is a great natural
catalogue of the neural control of vital functions (blood
circulation,
respiration, excretion).
"The entire central nervous system is involved in the maintenance of
internal homeostasis." (Pacak and Palkovits, 2001)
Neural Control of Glucose and Insulin Biosynthesis
A hypothalamic mechanism of regulation of glucose level, a
“glucostat” involving the endocrine pancreas, liver and adrenal
gland has been identified more than two decades ago (Benzo,
1983). The hypothalamus plays a critical role in hypoglycemia-
induced responses of adrenomedullary, sympathoneuronal, and
other systems (Pacak and Palkovits, 2001). Experimental lesions
of the PVN (hypothalamic paraventricular nucleus) result in
hypoglycemia. From PVN starts a descending pathway to the ILM
(intermedio-lateral cell column) and the dorsal vagal nucleus of the
vagus innervating VMH stimulates pancreatic secretion. Electrical
stimulation of the hypothalamus inhibits insulin secretion (Li et
al.,
2003)
Glucose sensors for detecting hypoglycemia have been identified in
the forebrain and the brainstem and especially in the VMH
(ventromedial
hypothalamus), which responds to the hypoglycemic state by activating
hormonal mechanisms, including secretion of glucagon and food intake.
The lateral and posterior parts of the hypothalamus release the
neuropeptide
orexin (Miyasaka et al., 2002), which stimulates food intake and via
the
vagal efferent nerve stimulates exocrine hormonal secretion in the
pancreas
(Wu et al., 2004). Ablation of the lateral hypothalamus inhibits the
vagal
pancreatic nerve firing and pancreatic secretion.
Stimulation of the parasympathetic nervous system leads to insulin
secretion
and inhibition of glucagon secretion, irrespective of whether the
stimuli occur
at the lateral hypothalamic nuclei, the motor nuclei of the vagus, or
the mixed
pancreatic nerves. Stimulation of the sympathetic nervous system or
application
of epinephrine likewise stimulates glucagon production and inhibit
insulin secretion.
(Norman and Litwack, 1997c)
Brain Control of Circadian Rhythms
Most metazoan (and plants too) are in possession of circadian
oscillators
that regulate circadian (24-hour) expression of genes in metazoans.
These
oscillators are ianccurate and it is a group of neurons in the SCN
(suprachiasmatic nucleus), the hypothalamic circadian pacemaker that,
by processing and integrating photic signals from the neural
photoreceptive
system, sends neurohormonal signals for restoring the circadian
order,
determining the 24-hour cycles of gene expression in cells throughout
the
metazoan body.
Expression of 8-10% of genes in peripheral organs is regulated in this
neurally
determined circadian mode (Storch et al., 2002).
Nerural Control of Body Temperature
Body temperature in metazoans is regulated by the preoptic area (POA)
of the hypothalamus, which also determines the set point for the
species
-specific temperature.
Peripheral temperature information is compared with central
temperature
information. As a result of this integration, the preoptic region
controls the
level of output for a set of thermoregulatory responses that are most
appropriate for the given internal and environmental temperatures.
(Boulant, 2000)
Remember that both the comparison of central and peripheral
temperatures
and the integration and processing of temperature information for
producing
the neural output that activates the mechanisms of thermoregulation
are
computational, hence nongenetic, epigenetic processes. There is no
evidence
that any genes are involved in the determination of set points for the
normal or
abnormal temperature in warm-blooded animals or in the mechanisms of
thermoregulation.
The Central Control of Body Mass
The body mass depends on the number and size of cells. The fact that
metazoans are able to keep, under normal conditions, a relatively
constant
weight while losing most of their cells many times during their
lifetime suggest
that there is a controls system that detects the loss of these cells
and sends
instructions for replacing them. There is evidence on the existence
in the
central nervous system of a set point for the body mass.
Intraperitoneal implantation of metabolically inert masses in the deer
mouse,
Peromyscus maniculatus, causes an equivalent compensatory loss of
body
weight. In the third day after the removal of the implant the animals
regained
the preexperimental body weight. Investigators argue that the changes
in the
body weight
"suggest the existence of a set point that is sensitive to changes in
the perception
of mass and that is transduced via neural pathways" (Adams et al.,
2001)
The mechanoreceptors located within muscles and tendons that have
afferent
pathways to cerebral cortex could provide the input necessary for
changing the
set point. Since the set point is located in the brain and is related
to the processing
of the sensory input by the brain, the growth processes adjusting the
body weight
to the changed set point must start with brain signals as well (Adams
et al., 2001).
Administration of some centrally acting substances, such as
sibutramine, lower body
weight set point and have found some use as medicaments for body
weight loss in
medicine. In response to administration of sibutramine rats increase
the sympathetic
activity, reset and decrease levels of NPY (neuropeptide Y) and POMC
(proopiomelanocortin). Since sibutramine is a serotonin reuptake
blocker, rats also
respond to its administration by elevating the extracellular level of
serotonin in the rat
hypothalamic arcuate nucleus, thus centrally inducing body weight loss
(Levin and
Dunn-Meynell, 2000).
Maintenance of Normal Obesity
In adult vertebrate organisms fluctuations in the body weight chiefly
result from
fluctuations of the fat storage. Maintenance of the normal weight
implies, among
other things, the existence of a mechanism that regulates the food
intake. This
regulation is very complex but, reduced to its essentials, the
regulatory mechanism
consists of specific neurons of the hypothalamic arcuate nucleus and
neurons in
another region of the brain. The arcuate nucleus contains two types of
neurons
eating-stimulating and eating-inhibiting neurons. Two different groups
of signals
are received by those neurons. In response to increases in fat store,
the appetite
-inhibiting neurons are activated and the appetite-stimulating neurons
in the arcuate
nucleus are inhibited. The signals from the appetite-inhibiting
neurons will dominate
the input in the neurons that control the food intake and energy
expenditure. Thus,
by decreasing the food intake and energy expenditure, the brain
induces decreases
the excess of fat in the body. Besides this long-term mechanism, in
vertebrates there
is a short-term mechanism based on the release of three kinds of
hormones, ghrelin
(released by the stomach), cholecystokinin, and the peptide hormone
PYY3-36,
released by the colon in an immediate response to food intake. The
input of these
three hormones is processed in the appetite-stimulating neurons of the
arcuate
nucleus and via the shown pathway stimulates food intake (Batterham et
al., 2002;
Schwartz and Morton, 2002; figure 1.13).
Details and other examples of the neural control of homeostasis in
metazoans are
presented in my book
Epigenetic Principles of Evolution
and in my website
nelsoncabej.com or http://www.epigeneticscomesofage.com
An unavoidable question from the above examples is:
How can the nervous system perform this function at the level of
individual cells?
Expression of the nonhousekeeping genes in metazoans is regulated by
extracellular factors such as hormones, growth factors other secreted
proteins, neurotransmitters, neuromodulators, etc. Given that all
these
factors are not randomly but orderly expressed and secreted in body
fluids,
information of some kind is spent for their secretion. Tracing back
the flow
of information for expression of nonhousekeeping genes, in a more
than
adequate number of scientifically verified cases, leads us to the
source of
this information in the central (diffuse in lower invertebrates)
nervous system.
A generalized neuroendocrine axis for the flow of that information
from the
central nervous system to nonhousekeeping genes in vertebrates looks
as follows:
Non-hypothalamic brain --> Hypothalamus --> Pituitary --> Terminal
endocrine glands -->Individual cells
N.C.
rnorman
> Epigenetic Control of Development, Homeostasis and Reproduction
>
> II. Neural Control of Homeostasis
>
> As pointed out in the first post of this series, the problems with
> metazoan life do not end with erection of their structure. In order
> to be able to reproduce themselves adult metazoans have to be
> able to maintain their thermodynamicaly unstable structure, i.e.
> to resist and conquer the thermodynamic forces of destruction.
> The maintenance of a stable internal environment, Claude
> Bernard's "fixete du milieu interieur" and Walter Cannon's
> "homeostasis", is considered here in a broader meaning, to
> include maintenance of the whole animal structure at both cellular
> and supracellular, organismic level.
<snip 200+ lines of stuff>
It should come as a surprise to absolutely nobody that the nervous
system is heavily involved with homeostasis. Bernard understood that
150 years ago and Cannon refined the idea almost 100 years ago. I
learned it 50 years ago and have taught it for more than 40. However
to call neurophysiology and endocrine physiology and cardiovascular
physiology and respiratory physiology and renal physiology examples of
"epigenetics" because most of their mechanisms are not genetic is
really pushing the notion of epigenetics far far beyond the breaking
point. It still remains true that the machinery of the nervous and
endocrine systems is built using the genetic information in the
developing organism and that there is no magic "epigenetic"
information transmitted from parent to offspring producing homeostatic
regulation. Homeostasis is a result of the building of an organized
animal body and the information necessary to build that organized body
is genetic.
rnorman
> nelsoncabej.com orhttp://www.epigeneticscomesofage.com
As usual we are speaking at cross purposes. It is very true that the
nervous system is involved in the tissue interactions involved in
early development. That does not mean that the nervous system ***as
an information processing system*** is involved. It only means that
the nervous cells interact with their neighbors in the same way that
epithelial cells interact with their neighbors. The information
processing capability of the nervous system is not involved, for
example, in the fact that blood vessels tend to parallel peripheral
nerve pathways. Since nerve and muscle necessarily function together
as a neuromuscular unit of action, it is no surprise that nerve and
muscle influence each other in development. And it is very clear that
in an already well developed animal life stage, the nervous system is
part of the regulatory machinery triggering events like metamorphosis.
None of this is related to epigenetics, though, unless you stretch the
notion of epigenetics to include any cellular function apart from the
molecular biology of DNA. Cells are motile, cells secrete, cells are
irritable (in the technical sense of responding electrically to
stimuli), cells are biochemical factories, cells transport material
across membranes; all these things are separate from genetics. None
of this is called epigenetics; it is called "cell physiology".
Nothing you have said and none of the citations you provide are in any
way connected to the notion that epigenetic information is transmitted
from parent to offspring and is involved with evolution in any way.
That is, except for the obvious fact that evolutionary mechanisms
acting through classical genetic and molecular biological mechanisms,
produce all the machinery that does all the really interesting and
important things you mention.
CNC...@aol.com
I think you are complicating a very simple question: Where the
information
for regulating physiological processes comes from?
I have presented a non-genetic, epigenetic mechanism of regulation
of physiological processes in which the information for regulating
these processes is generated in the central nervous system in the form
of
electric spike trains, which you seem to agree upon.
If you believe that the information for regulating your heart beat,
your
breathing rate or for determining the set point for your body
temperature
now that the human genome is sequenced you should be able to know
where these hypothetical genes are?
You have made it clear that you do not know either where these genes
are
or whether they exist at all.
Do you believe that the information (electrical spike trains)
for regulation of physiological processes is identical to the genetic
information for protein biosynthesis or is it a product of
transcription/
translation of that information?
I don't think you would make such a mistake.
N.C.
rnorman
I certainly don't make that mistake. I simply note that if A->B and B-
>C and C->A and you note the magnitude of each effect and calculate
the loop product of A on B on C back onto A and find that the
resulting "loop gain" is a negative number, then you find that you
have a negative feedback regulatory system where the setpoint is
determined by the details of how each link in the system works. In
some systems, there is one place in the loop which has the major
control over the setpoint. In the case of temperature regulation, as
is the case for so many homeostatic mechanisms in the body, that
location is in the hypothalamus. However we know that the function of
these cells results from the genetic programming that forms that cell
and forms the connections between that cell and neighboring cells.
Absolutely, there is no specific gene that says "make the temperature
98.6F = 37C" and there is no specific gene that says "make the blood
pressure 120/80 mm Hg = whatever the value is in proper SI units of
kPa". Rather, there are a whole complex of genes that say "make cells
in the temperature or cardiovascular regulatory regions of the
hypothalamus have these type of protein in these types of
concentrations and form these types of connections with the other
cells in the temperature/cardiovascular regulatory circuits". The
rest follows.
If you believe that there is some other source of information that
generates these regulatory systems, them produce that source and
demonstrate with evidence that they function to produce that results.
I don't think you make that kind of mistake. Instead, you argue
simply from incredulity that you don't understand how it all works
and therefore that there must be more to it than we know. Yes, there
is more to it. It is just that we have no reason to think that the
missing information is any kind of epigenetic inheritance.
CNC...@aol.com
This is not correct. It is not about any interactions. It is about
signal cascades regulating these processes during the development,
in cases of developmental plasticity, transgenerational developmental
plasticity and evolution. And signal cascades are unmistakable
indicators of the direction of the flow of information. The
information
in all these cases flows from the nervous system to the target
organs.
This is epigenetic information (it comes not from DNA and flows not
from DNA to RNAs to proteins.
>The information processing capability of the nervous system is not involved, for
> example, in the fact that blood vessels tend to parallel peripheral
> nerve pathways. Since nerve and muscle necessarily function together
> as a neuromuscular unit of action, it is no surprise that nerve and
> muscle influence each other in development.
The example of the sensory neurons that by secreting VEGFdetermine
cell differentiation and patterning of arteries in their vicinity is a
typical
case the of a structure on the template of a nerve. Let me quote once
again the investigator:
"Peripheral nerves provide a template that determines the organotypic
pattern of blood vessel branching and arterial differentiation in the
skin, via local secretion of VEGF. "(Mukoyama et al., 2002)
There is no interaction between nerves and blood vessels in this case
(in fact initially there areno blood vessels to interact).
The nerve secretes along its whole length secretes VEGF which induces
adjacent formation of blood vessels, thus serving as a template for
blood vessel formation. I believe we both agree that a template
provides information for formation of its copy rather than interacts
with the unexisting copy (remember DNA that serves
as a template for RNA synthesis).
The formation of the blood vessel is not a random
process (no random process could repeatedly produce the same pattern
as it occurs with blood cells) but a process for which the nerve
invests
epigenetic information.
>And it is very clear that
> in an already well developed animal life stage, the nervous system is
> part of the regulatory machinery triggering events like metamorphosis.
I doubt whether this general statement can argue anything.
> None of this is related to epigenetics, though, unless you stretch the
> notion of epigenetics to include any cellular function apart from the
> molecular biology of DNA. Cells are motile, cells secrete, cells are
> irritable (in the technical sense of responding electrically to
> stimuli), cells are biochemical factories, cells transport material
> across membranes; all these things are separate from genetics. None
> of this is called epigenetics; it is called "cell physiology".
This is a clear a (honest) distraction. It is irrelevant to our topic
of signals from
the brain that induce development of organs.
> Nothing you have said and none of the citations you provide are in any
> way connected to the notion that epigenetic information is transmitted
> from parent to offspring and is involved with evolution in any way.
This is another distraction. My intention in this post is to provide
you
a few of numerous examples of signals from the brain that induce
development of organs. I would like to see you to consider whether my
examples
prove my idea on the role of the central nervous system in the
development
rather than see irrelevant general statements.
Regards,
N.C.
rnorman
I have already acknowledged that there are interactions between (i.e.
"signals from") the nervous system and other tissues that influence
development. What you have never shown is that this has anthing in
the world to do with what is ordinarily called "epigenetics" as
opposed to, for example "developmental biology". You seem to think
that anything and everything that happens in cells and tissues and
organs and organisms that does not immediately involved DNA must
necessarily be epigenetic in nature.
Please answer this question. Do you believe that all these things
that you call "epigenetics" are factors that can be inherited from
parent to offspring and are involved in the process we call
evolution?
I
CNC...@aol.com
What you are ignoring is the fact that the setpoint is not randomly
fixed but is determined by the electrical activity of the brain not
by any genetic mechanism. This is the reason why setpoints
for physiological processes, for the composition of body fluids
(level of water, glucose, insulin, etc.), for body mass, and for
animal morphology in general are determined in the central
nervous system. If a genetic mechanism would play any role
in determining set points (a suggestion that to me seems to be
absurd) many other organs, which have the same genetic information,
would be responsible for determining the above setpoints.
>However we know that the function of
> these cells results from the genetic programming that forms
>that cell and forms the connections between that cell and neighboring cells.
No one, including you, knows that. Genetic information
is different from a "genetic program". If the genome would
contain a genetic program then any cell of our organisms would be
able to produce a human being, which is impossible
(zygote/eggs do that because they are provided with
the epigenetic information in form of parental cytoplasmic factors).
Connections between nerve cells in the hypothalamus
are not determined by genetic information (and I am sure this
is a lapsus on your part).
> Absolutely, there is no specific gene that says "make the temperature
> 98.6F = 37C" and there is no specific gene that says "make the blood
> pressure 120/80 mm Hg = whatever the value is in proper SI units of
> kPa". Rather, there are a whole complex of genes that say "make cells
> in the temperature or cardiovascular regulatory regions of the
> hypothalamus have these type of protein in these types of
> concentrations and form these types of connections with the other
> cells in the temperature/cardiovascular regulatory circuits". The
> rest follows.
Sorry, are you quoting?
Where is your source on "a whole complex of genes" doing that.
If someone would have discovered these genes I am sure
one Nobel prize would be less than he would deserve.
> If you believe that there is some other source of information that
> generates these regulatory systems, them produce that source and
> demonstrate with evidence that they function to produce that results.
> I don't think you make that kind of mistake. Instead, you argue
> simply from incredulity that you don't understand how it all works
> and therefore that there must be more to it than we know. Yes, there
> is more to it. It is just that we have no reason to think that the
> missing information is any kind of epigenetic inheritance.- Hide quoted text -
I have provided more than adequate evidence on the source
and generation of that epigenetic information but prefer to circumvent
as this response of yours clearly shows (in fact this is
the most wise thing you should do).
Regards,
N.C.
rnorman
<snip>
> I have provided more than adequate evidence on the source
> and generation of that epigenetic information but prefer to circumvent
> as this response of yours clearly shows (in fact this is
> the most wise thing you should do).
You have not answered the question I posed in another post on this
thread: Do you believe that all these things that you call
"epigenetics" are factors that can be inherited from
parent to offspring and are involved in the process we call evolution?
My response clearly shows that I believe you to apply the word
"epigenetics" to things very much different from what virtually all
biologists call "epigenetics". That is, epigenetics must relate to
HERITABLE characters through a mechanism distinct from the specific
nucleotide sequence in the genome. If you believe that your use
follows that definition, then I am failing to see any mention or
description of a plausible mechanisms for INHERITANCE distinct from
what we already know in classical genetics and molecular biology. The
way the enormous number of control and regulatory systems work within
one organism is an entirely different subject.