Specific modulation of ectodermal cell fates in Xenopus embryos by glycogen synthase kinase

Keiji Itoh, Terry L. Tang, Benjamin G. Neel, Sergei Y. Sokol

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

Shaggy is a downstream component of the wingless and Notch signaling pathways which operate during Drosophila development. To address the role of glycogen synthase kinase 3β (GSK3β), a mammalian homologue of Shaggy, in vertebrate embryogenesis, it was overexpressed in Xenopus embryos. Microinjection of rat GSK3β mRNA into animal ventral blastomeres of 8-cell-stage embryos triggered development of ectopic cement glands with an adjacent anterior neural tissue as evidenced by in situ hybridization with Xotx2, a fore/midbrain marker, and NCAM, a pan-neural marker. In contrast, animal dorsal injection of the same dose of GSK3β mRNA caused eye deficiencies, whereas vegetal injections had no pronounced effects on normal development. Using several mutated forms of rat GSK3β, we demonstrate that the observed phenotypes are dose-dependent and tightly correlate with GSK3β enzymatic activity. Lineage tracing experiments showed that the effects of GSK3β are cell autonomous and that ectopic cement glands and eye deficiencies arose directly from cells containing GSK3β mRNA. Molecular marker analysis of ectodermal explants overexpressing GSK3β has revealed activation of Xotx2 and of cement gland marker XAG-1, but expression of NCAM and XIF-3 was not detected. Phenotypic effects of mRNA encoding a Xenopus homologue of GSK3β were identical to those of rat GSK3β mRNA. We hypothesize that GSK3β mediates the initial steps of neural tissue specification and modulates anteroposterior ectodermal patterning via activation of Otx2 transcription. Our observations implicate GSK3β in signaling pathways operating during neural tissue development and during specification of anterior ectodermal cell fates.

Original languageEnglish
Pages (from-to)3979-3988
Number of pages10
JournalDevelopment (Cambridge)
Volume121
Issue number12
StatePublished - Dec 1995
Externally publishedYes

Keywords

  • Cement gland
  • Eye formation
  • Glycogen synthase kinase
  • Neural induction
  • Otx2

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