BIOL 426_ 4 - Polarity and Segmentation (Current Research)

BIOL 426_ 4 - Polarity and Segmentation (Current Research)...

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Polarity and Segmentation Part II: Homeobox Gene and Specification of Neuronal Identity
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In the vertebrate central nervous system, the developmental program begins with the differentiation of distinct classes of neurons from progenitor cells located at defined positions within the neural tube. -- Thomas Jessell
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Homeobox Gene Nkx2.2 and Specification of Neuronal Identity by Graded Sonic Hedgehog Signaling Briscoe et al., Nature 398: 622-627, 1999
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Background Sonic hedgehog: Shh induces ventral progenitor cells by repressing Pax3 and Pax7 expression. Shh then further interacts with other signaling system to generate ventral neurons and motor neurons. Graded Shh signaling within the ventral neural tube defines the identity and position of the distinct ventral neuronal subtypes. ventral dorsal secreted initially by notochord, and later also by floor plate cells.
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Shh Expression Jessell, Nature Reviews of Genetics, 1: 20-29, 2000. The fate of notochord? Degenerated Shh in notochord and floor plate
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Nkx2.2 Background Nkx2.2 is a homeobox gene, specifically expressed in a group of progenitor cells, called “X” domain, in-between floorplate and motor neuron region. “X” domain progenitors give rise to V3 ventral neurons, which express basic helix-loop-helix (bHLH) genes neurogenin-3 and Sim1 ( Single-minded homolog 1 ).
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Pax6 versus Nkx2.2 Pax6 is another homeobox gene, its expression in the ventral neural tube exhibits a ventral low- dorsal high gradient. Nkx2.2 expression is restricted to more ventral progenitors that do not express Pax6. These two populations of progenitors (expressing Pax6 or Nkx2.2) are established by graded Shh signaling. In Pax6 mutant mice, Nkx2.2 expression expands to dorsal region, suppresses the somatic motor neuron differentiation and induces more ventral V3 neurons. .
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What is the functional role of Nkx2.2 in
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BIOL 426_ 4 - Polarity and Segmentation (Current Research)...

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