Cell Biology Cooper Pdf Free Download
Edel Dieringer
As in the first edition, The Cell is focused on the molecularbiology of cells as a unifying theme, with specialized topics discussed throughoutthe book as examples of more general principles. Aspects of developmental biology,the immune system, the nervous system, and plant biology are thus discussed in theirbroader biological context in chapters covering areas such as genome structure, geneexpression, DNA rearrangements, the plasma membrane, cell signaling, and the cellcycle. Relationships between cell biology and medicine are similarly discussedthroughout the text, as well as being highlighted in the Molecular Medicine essaysthat are included as a special feature in each chapter. These discussions illustratethe striking impact of molecular and cellular biology on human health, and areintended to stimulate as well as inform those students interested in medicine.
Many neurons resemble other cells in developing embryos in migrating long distances before they differentiate. However, despite shared basic machinery, neurons differ from other migrating cells. Most dramatically, migrating neurons have a long and dynamic leading process, and may extend an axon from the rear while they migrate. Neurons must coordinate the extension and branching of their leading processes, cell movement with axon specification and extension, switching between actin and microtubule motors, and attachment and recycling of diverse adhesion proteins. New research is needed to fully understand how migration of such morphologically complicated cells is coordinated over space and time.
Janet Cooper, Ph.D., received a B.A. in biology from Culver-Stockton College in Canton, Missouri. She continued her studies at the University of Nebraska-Lincoln in the laboratory of Dr. Gary L. Smith., earning a Ph.D. in cell biology and genetics.
Her doctoral work involved the study of the somatomedin receptor in a human chondrosarcoma cell line. Following this work, Cooper worked at the Los Alamos National Laboratory examining the growth requirements of human fibroblasts and the effects of drugs on the Epidermal Growth Factor (EGF) receptor pathway.
She continued her postdoctoral studies at the University of Kansas Medical Center in the laboratory of Dr. Glen Andrews studying the promoter region of the Metallothionein gene in chickens. Upon the completion of her postdoctoral studies, Cooper began her teaching career at the University of Tulsa in Oklahoma and continued at Wayne State College in Nebraska before joining the biology department at Rockhurst University.
Cooper's main teaching responsibilities include Microbiology and Cell Biology. Her research interests involve undergraduate students and examine the effects of disinfectants on bacteria and bacterial viruses, as well as the growth requirements of S2 Drosophila cells in culture.
To gain a window into what evolution tells us about the developmental potential of the limb, we primarily focus on the three-toed jerboa, a small bipedal rodent that is closely related to the laboratory mouse and amenable to rearing in captivity. Compared to its quadrupedal relative, the jerboa has greatly elongated hindlimbs with three toes and metatarsals that fuse into a single bone. The unusual morphology of the jerboa skeleton allows us to ask what keeps one bone from growing into its adjacent neighbor? What mechanisms determine skeletal size and the relative proportions of individual elements? How are the correct numbers and positions of the digits established, and are the same mechanisms of digit loss redeployed in species that converge on similar morphologies (i.e. jerboas and horses, pigs and camels)? How can the forelimb and hindlimb evolve independently when both utilize the same developmental pathways? We apply classical embryology, cell biology, quantitative microscopy, high throughput sequence analysis, and mouse genetics in an integrative approach to understand these developmental mechanisms at the tissue and genome level.
Neuron migrations are broadly classified as radial (parallel to RG) or tangential (orthogonal to RG, either around the circumference of the neural tube or along its length). Radial migrations include the glial-guided locomotion phase and glia-independent somal translocation phase of cortical projection neurons (CPNs; Fig. 1 A, blue arrows and cells, steps 2 and 3), locomotion of cerebellar Purkinje cells (Fig. 1 B, blue), and locomotion of post-mitotic granule cells (GCs; Fig. 1 B, orange: note these cells are moving toward the ventricle). Tangential migrations include cortical interneurons in the marginal zone and intermediate zone (CINs; Fig. 1 A, red, steps 1 and 2), cerebellar granule cell precursors (Fig. 1 B, red), and pontine neurons (Fig. 1 B, purple). Some migrations are hard to classify: late-stage CINs switch from tangential to radial migration into the neocortex (Fig. 1 A, red, step 3), and CPNs migrate in random directions in the intermediate zone during their multipolar phase (Fig. 1 A, blue, step 1).
Migrations are termed neurophilic if they follow axons of other neurons, or gliophilic if they follow glia fibers. Gliophilic migrations include the locomotion phase of CPN migration (Fig. 1 A, blue, step 2), Purkinje cell migration (Fig. 1 B, blue, step 1), and part of the granule cell migration (Fig. 1 B, orange, step 2). Some stages of pontine neuron migration may be neurophilic. Some tangential migrations occur in direct contact with the extracellular matrix of the pia.
This short review presents an overview of neuron migration mechanisms for the cell biologist. For brevity, the short-range and long-range extracellular cues that guide neurons are not discussed; many of the same cues that guide neurons also guide axon growth cones and have been reviewed in depth recently (Kolodkin and Tessier-Lavigne, 2011; Vitriol and Zheng, 2012). Collective cell migrations and migrations in the peripheral nervous system are also ignored. Instead, we discuss the cellular machinery used by neurons migrating in the developing central nervous system. We focus on aspects that are peculiar or exaggerated in neurons compared with other cells: the long leading process, the linkage between the centrosome and nucleus, the use of microtubule motors and actomyosin to move the nucleus, and the variety of adhesion proteins and attachment points for traction. Not all neurons are alike, however, and exhibit almost as much variation in their migration as slime molds, keratinocytes, fibroblasts, and other cells commonly used as model systems. In addition to describing these differences, where possible we provide somewhat speculative unifying hypotheses to bring out common themes.
Similar principles may apply to cortical projection neurons (CPNs) in the intermediate zone of the developing neocortex. These cells are multipolar, extending and retracting unstable processes as they thread their way between tangentially aligned axons and radially aligned glial fibers. The cells change direction frequently, one process then another taking the leading role (Nadarajah et al., 2003; Tabata and Nakajima, 2003; Kriegstein and Noctor, 2004; Noctor et al., 2004; Sakakibara et al., 2013). The growth cones on individual processes may detect short-range or long-range signals and be differentially stabilized, like the branched processes of CINs (Fig. 2 B). Cytoskeletal forces may then pull the centrosome to the base of the dominant process, thereby steering the nucleus and selecting the direction for migration.
When a multipolar CPN nears the top of the intermediate zone, a radially oriented process becomes dominant, and the CPN migrates radially (Sakakibara et al., 2013). The CPN then migrates by locomotion, with the leading process entwined around radial glia (Rakic, 1972). The cells are called bipolar, although there is only one leading process and the trailing process is actually the axon, growing from the rear. The leading process is relatively unbranched and its tip moves forward continuously, without collapsing (Nadarajah et al., 2001). The leading process may help create a passage between the radial glia fiber and surrounding differentiating neurons. The base of the leading process, near the cell body, provides adhesion sites for moving the nucleus. Adhesion is discussed at the end of the review.
The role of the leading process therefore changes several times as CPNs journey from the ventricle to the marginal zone. In the intermediate zone there are multiple unstable processes, with the cell following whichever process is dominant at a particular time. Then, a single, stable leading process leads the way up the radial glia, and subsequently provides an attachment site during somal translocation.
Extracellular signals that regulate process stability are interpreted by intracellular machinery. Cell autonomous regulators of leading process stability and branching include the proneural basic helix-loop-helix gene, neurogenin2 (Ngn2; Hand et al., 2005). Ngn2 is induced soon after the last progenitor division, and stimulates a cascade of transcription events that lead ultimately to neuronal differentiation and the induction and repression of various migration genes (Ge et al., 2006). Mutation of a phosphorylation site in Ngn2, Y241, prevents migration but not differentiation (Hand et al., 2005). A key Ngn2 target gene encodes a small GTPase, Rnd2, which opposes RhoA (Heng et al., 2008). If Rnd2 is not induced, all phases of cell migration from the ventricle to the intermediate zone (multipolar and radial) are delayed. Cells lacking Rnd2 remain multipolar for an increased time, and when they start migrating radially they have a branched leading process. Somewhat paradoxically, a transcription inhibitor, RP58, is needed for the multipolar-to-radial transition, apparently by inhibiting Ngn2 and down-regulating Rnd2 (Ohtaka-Maruyama et al., 2013). Therefore, the correct ratio of Rnd2 and RhoA may promote the stabilization of a single leading process.
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