Gbx2 interacts with Otx2 and patterns the anterior-posterior axis during gastrulation in Xenopus

Ella Tour, Graciela Pillemer, Yosef Gruenbaum, Abraham Fainsod*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Anterior-posterior patterning of the embryo requires the activity of multiple homeobox genes among them Hox, caudal (Cdx, Xcad) and Otx2. During early gastrulation, Otx2 and Xcad2 establish a cross-regulatory network, which is an early event in the anterior-posterior patterning of the embryo. As gastrulation proceeds and the embryo elongates, a new domain forms, which expresses neither, Otx2 nor Xcad2 genes. Early transcription of the Xenopus Gbx2 homologue, Xgbx2a, is spatially restricted between Otx2 and Xcad2. When overexpressed, Otx2 and Xcad2 repress Xgbx2a transcription, suggesting their role in setting the early Xgbx2a expression domain. Homeobox genes have been shown to play crucial roles in the specification of the vertebrate brain. The border between the transcription domains of Otx2 and Gbx2 is the earliest known marker of the region where the midbrain/hindbrain boundary (MHB) organizer will develop. Xgbx2a is a negative regulator of Otx2 and a weak positive regulator of Xcad2. Using obligatory activator and repressor versions of Xgbx2a, we demonstrate that, during early embryogenesis, Xgbx2a acts as a transcriptional repressor. In addition, taking advantage of hormone-inducible versions of Xgbx2a and its antimorph, we show that the ability of Xgbx2a to induce head malformations is restricted to gastrula stages and correlates with its ability to repress Otx2 during the same developmental stages. We therefore suggest that the earliest known step of the MHB formation, the establishment of Otx2/Gbx2 boundary, takes place via mutual inhibitory interactions between these two genes and this process begins as early as at midgastrulation.

Original languageAmerican English
Pages (from-to)141-151
Number of pages11
JournalMechanisms of Development
Volume112
Issue number1-2
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
We wish to thank Christof Niehrs, Dale Frank, Hazel Sive, Herbert Steinbeisser, Randy Moon, Yi Rao and Tomas Pieler for probes and plasmids. We also thank Oded Khaner for his support during the course of this study. This work was supported in part by grants from the March of Dimes Birth Defects Foundation, Volkswagen Stiftung and The Israel Academy of Sciences to A.F. and by the Sheinbrun Foundation to Y.G.

Keywords

  • Cdx
  • Embryonic development
  • Gene regulation
  • Homeobox gene
  • Isthmic organizer
  • Midbrain/hindbrain boundary
  • Neural tube
  • Xenopus laevis
  • caudal

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