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16 cell -> 64 cell stage; ball of cells - blastocoel forms (hollow pocket inside) |
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| differentiation of regions begin through process of gastrulation |
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The differentiation of regions in the early embryonic stages.
Creates: the endoderm, ectoderm, and mesoderm |
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| The layer inbetween the "inner" and "outer" cell layers, aka the endoderm and ectoderm respectively |
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| the "dorsal lip" of the embryo which acts as both a neural inducer and an organizer of the entire body axis |
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| The process of the mesoderm to convert the overlying ectoderm into neural tissue |
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| The part of the embryonic ectoderm which develops into the neural tube |
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| Bone Morphogenetic Protein (BMP) |
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| molecule secreted by animal cap cells, makes cells epidermal, responds to TGFB receptors |
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| Prevents activation of TGFB receptors by BMP-4 causing the cells to become neural tissue. Capable of specifically inducing neural genes without inducing mesodermal genes. Expressed by the dorsal lips of the blastopore. Can hyperdorsalize embryos to give larger than normal brains |
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| Studies that provide information about the fate of the different neural tube regions. Fates of cells may fixed or may change. |
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| Tissue destined to form the nervous system, different parts of the neural plate are fated to become different parts of the nervous system |
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| The groove forming after the elongation of the neural plate which begins the folding and forming of the neural tube |
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| Becomes the peripheral nervous system, the gap between the neural tube and the ectoderm. |
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| Forms the central nervous system, gives rise to nearly all neurons and glia (along with the nerual crest) |
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| the neural plate elongates, forms a groove and then eventually folds over to form a neural tube |
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| Neural tube closure defect occurring at the CAUDAL end of the neural tube |
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| Neural tube closure defect occurring at the ROSTRAL end of the neural tube |
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| A hormone secreted by the notocord which induces the floor plate which then secretes SHH as well leading to the formation of motor neurons. Antagonized by BMP which leads to the formation of sensory neurons |
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| Proteins involved in the adhesion of developing neurons to glial cells |
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| The location of the neural epithelial cells which are "stem cells" of the nervous system |
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| The farthest point from the pial surface and location where neural epithelial cells undergo germination |
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| Mitosis of neural epithelial cells only occur at the ventricular surface |
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| Where neural epithelial cells undergo mitotic division (the ventricular surface) |
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| The dorsal side of the neural tube. Neurons here are primarily concerned with sensory functions |
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| Contains primarily motor neurons, extends from rostral mesencephalon to the spinal cord. |
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| Most ventral part of the neural tube. Will not form without the presence of the notochord releasing SHH, and forms motor neurons by releasing SHH itself. |
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| The most dorsal apsect of the neural tube, secretes BMP which antagonizes SHH and leads to the formation of sensory neurons |
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| The area of the neural tube nearest the ventricle. Contains mitotic figures. |
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| The area of the neural tube in between the ependymal zone and the marginal zone |
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| The area of the neural tube containing postmitotic neurons |
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| The combination of the ependymal zone and mantle zone in modern times. Where neural epithelial cells are in the cell cycle. |
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| The process where neurons are generated from neural stem cells and progenitor cells |
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| Created through the process of delamination and create ganglion mother cells (GMCs) themselves which each generate a pair of neurons or glia |
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| G1 (growth 1 phase, DNA synthesis occurs) -> S (DNA replication commences, DNA doubled)-> G2 (cell continues to grow) -> M Phase (Mitosis) |
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| Tritiated Thymidine Autoradiography |
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Definition
| Thymidine is used to label the S-phase of the cell cycle during the active phase of DNA replication. Show the progression of that generation of neural epithelial cells and where they end up. |
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| Future white matter, situated between the cortical plate and the subcortical plate |
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| Future cerebral cortex, situated superficially to the ventricular zone. The majority of neurons in the cerebral cortex accumulate in this layer |
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| Future cell sparse cortical layer 1. The most superficial layer of the cerebral cortex near the pial surface. Made up of Cajal-Retzius cells |
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| Gradient of Corticogenesis |
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| Inside-out. "Older" cells are situated deeper within the cortex while "newer" born cells are situated more superficially |
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| Provide a scaffold to guide newly generated cortical neurons to their destinations, range from the ventricular zone to the pial surface |
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| protein responsible for the attachment of neurons to radial glial cells (allows migration). Secreted by neuroblasts |
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| Make up the marginal zone, turn on a gene named "reelin" which is necessary to form the inside-out gradient of the cortex |
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| Can be used to label clones of cells. Can also be used to transfer genes. |
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| All the cells of a column in the cortical plate are not necessarily from the same point (radial glial fiber) in the ventricular zone. A degree of dispersion occurs |
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| inject lacZ bacterial gene as linear DNA into male pronucleus. Creates blue mouse and offspring if male due to being situated on the X chromosome. Females show a "salt & pepper" effect. |
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| Gene which expressed β-galactosidase which is a reporter marker |
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| Blue Mice Experiment. Females have random inactivation of one X chromosome (visible as Barr bodies) such as in the Calico cat |
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| Facilitated via astrotactin and radial glial cells |
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| Tangential Dispersion of clones |
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| X-inactivation mosaic mice |
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| Olfactory bulb (rostral migration system), Cerebellum (external granule layer) |
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| Mechanisms for tangential migration |
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| Axonal pathways, cells migrate via "chain migration" and are influenced by "SLIT" proteins along its course |
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| Cells int eh septum which secrete the SLIT protein. creates a migratory effect away from the septum for migratory neuronal cells creating the rostral migratory system. |
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| Rostral Migratory Stystem |
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Definition
| Cells going from the lateral wall of the ventricular zone to the olfactory bulb without axons or radial glia. Contains cells witha gene which expressed "prokinectin receptors". Necessary for the formation of the olfactory bulb |
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| Extracellular Matrix Molecules |
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Definition
| Laminin and fibronectin are secreted beneath the peal surface and act as an attractant for neural crest migration |
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Definition
The neural crest gives rise to the autonomic and sensory ganglia of the PNS. Different segments of the neural crest give rise to the sympathetic (noradrenergic) or the parasympathetic (cholinergic) ganglia of the ANS
Somites 2-7 cholinergic neurons (PNS) is made
Somites 7-18 adrenergic neurons (SNS) are made |
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| A more defined type of stem cell but which may be able to differentiate into various types of cells. (Ex. Glial progenitor cells can differentiate into any type of glial cell) |
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| Future generations, descendants of a particular progenitor cell (clones) |
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| Clonal relationships analyzed using: |
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Definition
Replication-deficient retroviral (reporter) gene transfer
Single cell injection
Chimeric production
X-inactivation mosaics |
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| multipotent progenitors cells can give rise to progeny from various different lineages. Ex. a Ganglion Mother Cell can become neurons or glial cells |
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| Types of Progenitor Cells in Telencephalon |
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| Astrocytes, Oligodendrocytes, Pyramidal Neurons, Nonpyramidal neurons |
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| How to create an Aggragated Chimeric Mouse |
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Definition
| Take two morulas at embryonic day two of one pigmented embryo and one unpigmented. "Msh" the morulas together to create a 16-cell morula which will develop normally |
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| When do cells acquire their fate? |
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Definition
| Cells will change their fate if transplanted in the S phase, if the cell goes through its final mitotic division before transplantation however it will retain its original fate |
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| Why does only one daughter cell except the new fate? |
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Definition
| During the neurogenesis phase of proliferation cells divide horizontally rather than vertically, meaning only one daughter cell will remain in contact with the ventricular surface |
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| Cell intrinsic vs Cell extrinsic determinants |
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| Cells change and mature over time (the cortical progenitor cell) therefore you cannot transplant a progenitor cell that should be fated for layer 2 (older, more superficial) into an enviornment producing layer 6 cells (newer, more deep cells) |
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| Symmetric vs Asymmetric Divisions |
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Definition
Asymmetric: a mitotic cell divides into two cells, one mitotic cell and one specialized (no longer dividing)
Symmetric: A mitotic cell divides into two mitotic cells, one of which goes into two specialized cells and the other which goes to another two mitotic cells. (staggered) |
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| a protein that is necessary for cells to remain in teh cell cycle, therefore if a cell divides horizontally the "top" daughter cell will leave the cell cycle. |
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If a knock-out mice without the Numb protein then many cells will leave the cell cycle too early and differentiate.
Underdeveloped, smaller brain, neural tube closure defects |
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| a gene which when over expressed causes a much larger cortex to develop. Possibly creates extra symmetric divisions before asymmetric. |
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| Differentiation can be through various means: |
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Definition
| morphologically, biochemically, pharmacologically, cytoskeleton, gene expression |
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| How many types of cells are in the cerebellar cortex |
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Definition
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| Morphological differentiation |
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Definition
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| Pharmacological differentiation |
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| Neurotransmitter synthesis, receptor expression |
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| Cytological or Biochemical differentiation |
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Definition
| cytoskeletal or cytoplasmic proteins, signal transduction proteins |
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| When do granule cells differentiate? |
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Definition
| Before reaching its ultimate environment, therefore this cell does not receive a signal for differentiation in its final environment |
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| Differentiation before completing migration: |
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Definition
| Cerebellar granule cells, retinal ganglion cells, callosally projecting cortical cells, DA-expressing substantia nigra cells, ChAT-expressing basal forebrain cells |
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Definition
The granular layer. Infragranular layers (below 4) project axons to subcortical areas, supragranular layers (above 4) project to cortical areas.
Cells are often "stellate" (star-shaped) |
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| Where are pyramidal cells located? |
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Definition
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| Neuroblast response to environmental signals |
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| Not allneuroblasts respond to environmental signals in the same manner, may be due to receptor expression |
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| an axon which travels from the cortical plate down into the white matter, and to the opposite hemisphere and into the other cortical plate |
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| When do cells begin to differentiate |
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| En route to their final destinations therefore they cannot be receiving the signals simply from the final destination |
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| determined before the cell reaches its destination |
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| Stages of neuronal cell development: |
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| lamellipodia -> minor process -> axonal outgrowth -> dendritic outgrowth |
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| Exist at the tip of the axon and dendrites and create the path of growth "cell on a leash" |
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| present where growth cones exist |
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| microspikes, the tips of the growth cone |
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| veil, inbetween the filopodia |
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| made up of tubulin, int he axon are only made at the outertip of the axon |
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| depolymerizes actin and cases axons to turn away |
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| stabilizes microtubules and causes axons in turn toward |
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| transient structure at the midline which may be critical for pioneering growth cones from one hemisphere to another |
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| homophilic binding, binding of extracellular matrix molecules, contact repulsion/inhibition, chemotaxis |
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Definition
| N-CAM, L1, TAG-1, cadherins |
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| Binding of extracellular matrix |
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Definition
| integrin receptors, laminin & fibronectin |
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| Contact repulsion/inhibition |
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Definition
| EphA receptors and ephrin A ligands, oligodendrocytes, myelin |
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| chemoattractants and chemorepellants |
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| Neural-Cell Adhesion Molecule, promotes neural outgrowth but not necessarily directionality |
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| neural glial-cell adhesion molecule (neurite to glial interaction) |
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| made of alpha and beta dimers to make up different types of integrin receptors |
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| secreted by the septum and repels olfactory bulb axons. The olfactory bulb secretes ROBO which is a receptor to slit proteins |
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| chemical repellant, causes axons to grow into the corpus callosum. Knockout mice for draxin will not form a corpus callosum |
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| gene, highly homologous, secreted by the floor plate |
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| deleted in colo-rectal cncer gene |
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| molecule facilitates homophilic migration |
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| commissural neurons pass through the floor plate, down regulate their TAG1, then 90 degree turn to travel longitudinally, then upregulate their L1 |
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| PKa inhibitors effect on Netrin |
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Definition
| PKa inhibitors lower intracellular cAMP levels, changing the response to Netrin from one of chemoattraction to chemorepulsion |
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| Growth on Laminin for growth cones |
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Definition
| lowers cAMP in the growth cone and converts the response to Netrin |
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Definition
| frizzle 3, is the receptor for wnt 4, fz3 knockout mice would experience undiscriminable growth cones |
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Definition
| homophilic binding molecule, contributes to growth of later developing cells |
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| found in multiple places in the NS, highly concentrated in the retina. Growth cones may not like to gro win presence of CSPG's |
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| the area of the optic chaism where two optic nerves seperate and create dorsal and ventral axons |
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| What causes the separation of dorsal and ventral optic nerve axons? |
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| Something in the wall of the diencephalon. The wall of the neuroepithelium helps guide optic nerve growth, the optic tectum secretes something to attract optic nerves as well |
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| optic axons go through this to reestablish order for the dorsal and ventral axons |
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| wnt4 gradient and commissural neurons |
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Definition
| After moving through the floor plate commissural neurons will turn and move along the wnt4 gradient (posterior -> anterior) |
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Definition
| express Eph B receptors, do not cross the midline. The chiasmatic midline region expresses Ephrin B2 ligands |
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| Knocking out the Eph B1 gene causes what? |
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Definition
| It reduces the size of the uncrossed projection, aka more RGC's go to the ipsilateral side |
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Definition
| Islet 2 is a transcription factor which controls the process of EPhB receptor expression |
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| Difference between cold blooded and warm blooded animals RGC's? |
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Definition
| Cold blooded animals can regenerate RGC's while warm blooded animals cannot |
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| expressed in the temporal retina and modulates the RGC process (is only expressed by EphB2). Repressed by Isl2 which would cause EphB receptor expression |
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Definition
| Present on the tectum. High on caudal end and low in rostral end |
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| RGCs from the nasal retina grow indiscriminately while RGCs from the temporal retina grow in a specific way which discriminates between rostral and caudal tectum. Temporal RGCs do not like growing on caudal fragments of the tectum. |
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