You recently identified a new mutation in Xenopus. We don’t know which gene is m

Question

You recently identified a new mutation in Xenopus. We don’t know which gene is mutated, but when you observe the mutant embryo it appears to gastrulate, elongate, and make it through neurulation. Then the embryos die. The anterior has no sensory structures and it is difficult to determine to what degree the head is missing/misformed based on the morphology alone.

a) What process do you think might be disrupted?

b) Describe experiments you would do to further characterize the mutant phenotype and provide a better idea about which pathways are disrupted.

Explanation / Answer

a. We can examine the activity of a gene named Bone morphogenetic protein 15 (BMP15) in order to study its role in misformed anterior portion of Xenopus embryo. BMP 15 belongs to superfamily of signaling ligands named as transforming growth factor or TGF .

b. Loss-of-function experiments using morpholinos and experiments involving naturally occurring human BMP15 dominant-negative mutant (BMP15-Y235C) give a better idea as to which pathways are disrupted.

BMP15 strongly inhibits BMP-responsive element or BRE response induced by BMP4 and blocks the phosphorylation and activation of Smad1/5/8 MH2-domain which leads to embryos lacking head.

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