Practice question

Lithium chloride is classic vegetalizing agent discovered by Herbst in sea urchin experiments. Mechanistically it directly inhibits glycogen synthase kinase-3β (GSK-3β), central component of Axin-APC destruction complex that phosphorylates β-catenin targeting it for ubiquitin-proteasome degradation. Inhibition stabilizes β-catenin, causing its cytoplasmic accumulation and translocation into nuclei even in animal blastomeres normally destined for ectoderm. Resulting ectopic activation of vegetal gene network expands endomesodermal domain at expense of ectoderm producing exogastrulae. Phenotype resembles Wnt overactivation. Therefore lithium exposure increases β-catenin nuclear localization, converting presumptive ectoderm to endoderm.