Xenopus Meis3 protein lies at a nexus downstream to Zic1 and Pax3 proteins, regulating multiple cell-fates during early nervous system development

Yoni E. Gutkovich, Rachel Ofir, Yaniv M. Elkouby, Charna Dibner, Aharon Gefen, Sarah Elias, Dale Frank*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

In Xenopus embryos, XMeis3 protein activity is required for normal hindbrain formation. Our results show that XMeis3 protein knock down also causes a loss of primary neuron and neural crest cell lineages, without altering expression of Zic, Sox or Pax3 genes. Knock down or inhibition of the Pax3, Zic1 or Zic5 protein activities extinguishes embryonic expression of the XMeis3 gene, as well as triggering the loss of hindbrain, neural crest and primary neuron cell fates. Ectopic XMeis3 expression can rescue the Zic knock down phenotype. HoxD1 is an XMeis3 direct-target gene, and ectopic HoxD1 expression rescues cell fate losses in either XMeis3 or Zic protein knock down embryos. FGF3 and FGF8 are direct target genes of XMeis3 protein and their expression is lost in XMeis3 morphant embryos. In the genetic cascade controlling embryonic neural cell specification, XMeis3 lies below general-neuralizing, but upstream of FGF and regional-specific genes. Thus, XMeis3 protein is positioned at a key regulatory point, simultaneously regulating multiple neural cell fates during early vertebrate nervous system development.

Original languageAmerican English
Pages (from-to)50-62
Number of pages13
JournalDevelopmental Biology
Volume338
Issue number1
DOIs
StatePublished - 1 Feb 2010
Externally publishedYes

Bibliographical note

Funding Information:
We thank Drs. Y. Sasai, N. Sasai, J. Aruga, R.B. Fletcher, A.H. Monsoro-Burq, K.J. Liu, and T. Grammer for plasmids and MOs. D. F. was supported by grants from the Israel Science Foundation (197/05), Israel Cancer Research Fund, B. and G. Greenberg Technion Research Fund for the Advancement of Research and the F.F. Technion Research Fund. R.O. was supported by a Lady Davis Foundation postdoctoral fellowship.

Keywords

  • FGF
  • Hindbrain
  • Neural crest
  • Pax3
  • Primary neurons
  • XMeis3
  • Xenopus
  • Zic1

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