Otx2 can activate the isthmic organizer genetic network in the Xenopus embryo

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Development and differentiation of the vertebrate caudal midbrain and anterior hindbrain are dependent on the isthmic organizer signals at the midbrain/hindbrain boundary (MHB). The future MHB forms at the boundary between the Otx2 and Gbx2 expression domains. Recent studies in mice and chick suggested that the apposition of Otx2- and Gbx2-expressing cells is instrumental for the positioning and early induction of the MHB genetic cascade. We show that Otx2 and Gbx2 perform different roles in this process. We find that ectopically expressed Otx2 on its own can induce a substantial part of the MHB genetic network, namely En2, Wnt1, Pax-2, Fgf8 and Gbx2, in a concentration-dependent manner. This induction does not require protein synthesis and ends during neurulation. In contrast, Gbx2 is a negative regulator of Otx2 and the MHB genes. Based on the temporal patterns of expression of the genes involved, we propose that Otx2 might be the early inducer of the isthmic organizer genetic network while Gbx2 restricts Otx2 expression along the anterior-posterior axis and establishes an Otx2 gradient.

Original languageAmerican English
Pages (from-to)3-13
Number of pages11
JournalMechanisms of Development
Issue number1-2
StatePublished - Jan 2002

Bibliographical note

Funding Information:
We wish to thank Andre Brändli, Dale Frank, Herbert Steinbeisser, Randy Moon and Jonathan Slack for probes and plasmids. We are grateful to Hazel Sive, who provided us with the hormone-inducible versions of Otx2 . We thank Oded Khaner for his support during the course of the work and William McGinnis for comments on this manuscript. 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.


  • Embryonic development
  • Gastrulation
  • Gbx2
  • Gene regulation
  • Homeobox genes
  • Midbrain/hindbrain boundary
  • Neural tube
  • Neurula
  • Xenopus laevis


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