Xenopus XsalF: anterior neuroectodermal specification by attenuating cellular responsiveness to Wnt signaling

Dev Cell. 2004 Jul;7(1):95-106. doi: 10.1016/j.devcel.2004.06.004.

Abstract

Here we show that XsalF, a frog homolog of the Drosophila homeotic selector spalt, plays an essential role for the forebrain/midbrain determination in Xenopus. XsalF overexpression expands the domain of forebrain/midbrain genes and suppresses midbrain/hindbrain boundary (MHB) markers and anterior hindbrain genes. Loss-of-function studies show that XsalF is essential for the expression of the forebrain/midbrain genes and for the repression of the caudal genes. Interestingly, XsalF functions by antagonizing canonical Wnt signaling, which promotes caudalization of neural tissues. XsalF is required for anterior-specific expressions of GSK3beta and Tcf3, genes encoding antagonistic effectors of Wnt signaling. Loss-of-function phenotypes of GSK3beta and Tcf3 mimic those of XsalF while injections of GSK3beta and Tcf3 rescue loss-of-function phenotypes of XsalF. These findings suggest that the forebrain/midbrain-specific gene XsalF negatively controls cellular responsiveness to posteriorizing Wnt signals by regulating region-specific GSK3beta and Tcf3 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / embryology*
  • Brain / metabolism*
  • Cell Lineage / genetics
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • Drosophila Proteins
  • Ectoderm / cytology
  • Ectoderm / metabolism*
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental / genetics
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 / pharmacology
  • Glycogen Synthase Kinase 3 beta
  • HMGB Proteins / genetics
  • HMGB Proteins / metabolism
  • HMGB Proteins / pharmacology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mesencephalon / cytology
  • Mesencephalon / embryology
  • Mesencephalon / metabolism
  • Molecular Sequence Data
  • Mutation / genetics
  • Phenotype
  • Prosencephalon / cytology
  • Prosencephalon / embryology
  • Prosencephalon / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / metabolism
  • RNA, Messenger / pharmacology
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Signal Transduction / genetics
  • TCF Transcription Factors
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors / genetics
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*
  • Transcription Factors / pharmacology
  • Wnt Proteins
  • Xenopus Proteins / genetics
  • Xenopus Proteins / isolation & purification
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / embryology*
  • Xenopus laevis / metabolism*
  • Zinc Fingers / genetics

Substances

  • DNA, Complementary
  • Drosophila Proteins
  • HMGB Proteins
  • Homeodomain Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • SALL2 protein, Xenopus
  • TCF Transcription Factors
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors
  • Wnt Proteins
  • Xenopus Proteins
  • salm protein, Drosophila
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3

Associated data

  • GENBANK/AY508953
  • GENBANK/AY508954