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Lecture4Notes - The Homeobox (hox) genes! Developmental...

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1 Karina S. Cramer [email protected] 10/4/11 Developmental Neurobiology N152 The Homeobox ( hox ) genes Include a conserved 60 amino acid region, the homeodomain. Ancestral complex duplicated twice during mammalian evolution to give 4 clusters. Position along chromosome (3 ` -5 ` ) is related to expression along A-P axis. The most l posterior z of the genes expressed in a cell dominates and drives down expression of previously activated l anterior z genes in that segment. The Homeobox ( hox ) genes Similar function in vertebrates and invertebrates: Control of segment identity “Default” seems to be anterior segments for both Upstream control of expression appears to differ Invertebrates: Results from transcription factor cascades starting with maternal effect genes Vertebrates: Retinoic acid gradients Deletion of Hoxa1 leads to loss of r4 Early expression begins in rhombomere 4 Expression shifts caudally to r5 Mutations lead to loss of r5 and reduction of r4 Makki & Capecchi, 2011
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2 Deletion of Hoxa1 respeciFes segment identity Deletion of Hoxa1 causes loss of r5 and reduction of r4. Result is loss of abducens motor neurons and fewer facial motor neurons. Some of the neurons in the l rx z region take on other fates. Human mutations in Hoxa1 Syndromes affect areas in hindbrain region: Eye movements DifFculty breathing ±acial weakness Vocal chord paralysis DifFculty swallowing Deafness (otocyst) Cardiac function (failure of neural crest cell migration) ±igure 22-80a Molecular Biology of the Cel (© Garland Science 2008) Sonic hedgehog and BMPs help to establish dorsal-ventral polarity Combinations of transcription factors deFne groups of neurons in regions of the spinal cord Neurogenesis Generation of neurons and glia Produced by division of progenitor cells: neurons are l born z when they undergo their Fnal mitotic division. Several levels of control to regulate the number of neurons and glia in the brain Many of these controls regulate the cell cycle
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3 Cell Cycle G 1 phase: Biosynthesis, preparation for DNA replication S phase: DNA synthesis G 2 phase: Protein synthesis, preparation for mitosis M phase: mitosis (G 1 + S + G 2 is Interphase) G 0 phase: quiescent; cell has left cycle and stopped dividing. Invertebrates Nematodes : Stereotyped cell lineages give invariant numbers of neurons. 959 somatic cells, of which 302 are neurons Mutants that cause deviations have led to identiFcation of several classes of genes that work in similar ways in vertebrates. Invertebrates Drosophila (and other arthropods): Stereotyped number of neuroblasts, but more variation than in nematodes Neuroblasts undergo stereotyped lineages ±ind identiFed neurons in ganglia Vertebrate Neurogenesis Neural tube starts out only one cell thick, then thickens as cells divide. Proliferating cells are found at the ventricular zone and the nucleus
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This note was uploaded on 12/13/2011 for the course BIOSCI 93 taught by Professor Staff during the Fall '11 term at UC Irvine.

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Lecture4Notes - The Homeobox (hox) genes! Developmental...

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