Biology of Stem Cells
Biology of Stem Cells MCDB 4615
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This 3 page Class Notes was uploaded by Mrs. Willis Mante on Thursday October 29, 2015. The Class Notes belongs to MCDB 4615 at University of Colorado at Boulder taught by Staff in Fall. Since its upload, it has received 17 views. For similar materials see /class/231844/mcdb-4615-university-of-colorado-at-boulder in Molecular, Cellular And Developmental Biology at University of Colorado at Boulder.
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Date Created: 10/29/15
MCDB 4620 VERTEBRATE DEVELOPMENTAL BIOLOGY LECTURE NOTES 101502 Development of the cerebral cortex and eye Reading Gilbert pp 389395 400403 Initial organization of the brain The brain develops from the neural tube extending along AP axis of embryo Neurons mature in an quotinside ou quot fashionventricular layer is dividing layer Cells migrate out from this layer into the mantle layer cell rich grey where they begin to differentiate and send axons out into the marginal layer cell poor white There are two major classes of cells in the nervous system neurons and glia Figs 12211224 l neuronsthe electrically excitable cells that conduct impulses organization of neurons a dendrites receive impulses FROM other cells input b axons transmit impulses TO other cells output c growth cone at the tip of the axon is a specialized structure that senses cues in its environment and guides the axon to make the proper connection to its target 2 gliasupport cells such as oligodenderocytes which produce myelin that surrounds the axons Development and organization of the cerebral cortex In all regions of the developing brain proliferation takes place in the ventricular zone which is immediately adjacent to the lumen Fig 1215 a cell bodies migrate from apical to basal surface of the tube as they go through the stages of mitosis interkinetic nuclear migration b Symmetric vs asymmetric divisions are correlated with a cell s decision to keep dividing within the ventricular zone or to stop dividing and begin differentiating Asymmetric divisions separate one daughter cell from the ventricular surface that daughter migrates away whereas symmetric divisions leave them both in contact with it Possible molecules involved are the transcription factor BFl and the juxtacrine signaling molecule Notch Once a cell stops dividing it is quotbomquot or has its quotbirthdayquot Studies of how the cerebral cortex gets organized depend on being able to identify the cells as they are born Functional organization of the cerebral cortex 4 lobes frontal parietal temporal occipitalieach region carries out a specialized function Laminar organization of the cortical plate 6 layers Superficial layers 123 project to other cortical targets while deep layers 456 project to subcortical targets like the thalamus Organization of the functional areas Radial and tangential migrationimost cortical neurons migrate radially directly perpendicular to their origin in the ventricular zone but 1020 migrate tangentially Lineage tracing of neuronal progenitors to see determine fate Progenitors are labeled with DiI or with a retroviral marker that can be visualized later Clones of cells ie cells that have all derived from the original progenitor are scattered throughout the cortex both radially and tangentially At rst researchers postulated that the progenitors were migrating but more recent evidence suggests that the postmitotic neurons migrate Organization of the laminae o The 6 cortical layers are formed in an insideou pattern of migration Fig 1219 the rst layer of neurons to form is the deepest layer 56 In other words the cells that leave the ventricular zone rst migrate the shortest distance to layer 56 while cells that are born later migrate out to the more super cial layers 123 How are the fates of these cells determined how do they know which layer to go to Transplantation of cortical precursors has demonstrated several features of laminar determination Fig 1220 1 EARLY birthdate determines fate Progenitor cells that would normally migrate to deep layers can be induced to migrate to super cial layers If they undergo their nal S phase in a different environment older host they can change their fate to that of the host cells super cial layer migration layers 123 The critical factor appears to be where the cells undergo their nal S phase nal duplication of DNA before nal mitotic division Cells that have undergone their nal S phase in their native environment cannot change their fate 2 LATER the possible fate of the cells becomes restricted Thus at later developmental stages laminar fate has already been determined and cannot be reprogrammed When late stage progenitors that would normally migrate to super cial layers are transplanted into earlier stage hosts P1 postnatal day 1 cells transplanted to an E29 embryonic day 29 host the transplanted cells cannot change their fate even if they undergo their nal S phase in the new environment They are irreversibly committed to migrate to super cial layers 3 CELLCELL CONTACT are important in determining the fate of cortical neurons Cellcell communication speci cally promotes deep layer fates Prospective deep layer cells require contact with other prospective deep layer cells in order to migrate to layers 56 If they are cultured as dispersed cells signaling molecules not prsent at high concentrations they can migrate to more super cial layers while if they are cultured intact communicating with their neighbors they migrate to deep layers It has been proposed that two molecules Otxl and Wnt 7b may be involved in the determination of deep layer cells since these molecules are expressed only in the deep layers 56 ofthe cortex Development of the eye if there39s time otherwise I will cover this in the axon guidance lecture do not study this material for today39s quiz Formation of the optic vesicle The eye eld is de ned in the anterior neural plate Outpocketing of the brain itself at the level of the diencephalon makes the primary optic vesicle 1227 The optic vesicle then contacts the ectoderm of the head inducing the lens placode The medial optic vesicle narrows to become the optic stalk while the lateral part of the optic vesicle is pushed in or invaginates to become the optic cup The outer layer of the optic cup will become the RPE and the inner layer will become the neural retina The transcription factor Rx is required for formation of the optic vesicle Expression is present in two lateral patches in the anterior neural plate and in the optic vesicle Neural retina and pigmented retina differentiation of these two structures seems to be entertwined FGF l and 2 acidic and basic generally promote retinal differentiation at the expense of RPE high levels of FGF can induce the RPE to make retina BMP7 null mice have impaired development of both retina and RPE remember BMP7 also required for lens formation The neurotrophins BDNF and NT3 are used for maintenance of both structuresineural retina does not survive without RPE These two molecules are also used during the differentiation of the sensory epithelium in the auditory system Differentiation of the neural retina 1229 Mueller glia neurons cones and rods photoreceptors interneurons biopolar horizontal amacrine and retinal ganglion cells RGC RGCs differentiate rst photoreceptors last A single progenitor cell can give rise to cells in all layers of the retina both glia and neurons Fig 1230 Retroviral labeling of single progenitor cells Light has to travel through all the cell layers to the back of the eye where it is received and transduced into an electrical signal by the photoreceptors The information is then sent back out to the RGCs which send axons to the optic nerve to the brain and ultimately to the tectum or the equivalent superior colliculus in mammals for processing
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