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The neural tube is patterned along the dorsal-ventral axis by opposing morphogen

ID: 40640 • Letter: T

Question

The neural tube is patterned along the dorsal-ventral axis by opposing morphogen gradients. What is the phenotype that would be produced by the following manipulations? In each case explain your answer in the context of the proposed dorsal-ventral mechanism and provide a molecular technique that would allow you to asses the cell fates.

a. The notochord is transplanted from the ventral floor plate to the lateral side between the neural tube and the somites.

b.An embryo where Smad1 and 5 are knocked out in the dorsal neural tube right after the neural tube closes and splits off from the epidermal cells.

c. An embryo everexpressing a transcriptionally active form of Ci/Gli throughout the neural tube.

Explanation / Answer

eight murine Smad genes identified, with Smads 1, 5, and 8 having been shown to be responsive to BMP signals. Once BMPs are secreted, they bind to type II BMP receptors. These then recruit and phosphorylate type I receptors within intracellular GS (glycine-serine-rich) domains. Type I receptors in turn phosphorylate Smad1, 5, or 8 at the C terminus at a conserved SSXS motif. Smad4, the co-Smad, can then multimerize with the BMP-regulated Smads to facilitate their translocation into the nucleus to either transcriptionally activate or repress target genes

Smad1 null homozygotes die at embryonic day due to defects in the formation of the allantois and placentaSmad5 null homozygotes also die due to angiogenic failure, mesenchymal apoptosis, and other defects.

ChIP assay in Gli1-overexpressing MEF cells showed a significant reduction of the recruitment of Gli1 into the promoter of Ptch1 gene

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