PUBLICATION

Mixer/Bon and FoxH1/Sur have overlapping and divergent roles in Nodal signaling and mesendoderm induction

Authors
Kunwar, P.S., Zimmerman, S., Bennett, J.T., Chen, Y., Whitman, M., and Schier, A.F.
ID
ZDB-PUB-031009-7
Date
2003
Source
Development (Cambridge, England)   130(23): 5589-5599 (Journal)
Registered Authors
Bennett, Jimmy, Chen, Yu, Schier, Alexander, Zimmerman, Steve
Keywords
nodal, Smad, mesoderm, endoderm, FoxH1, mix, zebrafish
MeSH Terms
  • Animals
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Embryonic Induction*
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism*
  • In Situ Hybridization
  • Mesoderm/physiology*
  • Morphogenesis
  • Nodal Protein
  • Oligonucleotides, Antisense/metabolism
  • Signal Transduction/physiology*
  • Smad2 Protein
  • Trans-Activators/metabolism
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/metabolism
  • Zebrafish Proteins
PubMed
14522874 Full text @ Development
Abstract
Transcription factors belonging to the FoxH1 and Mixer families are required for facets of Nodal signaling during vertebrate mesendoderm induction. Here, we analyze whether zebrafish proteins related to FoxH1 [Schmalspur (Sur)] and Mixer [Bonnie and clyde (Bon)] act within or downstream of the Nodal signaling pathway, test whether these two factors have additive or overlapping activities, and determine whether FoxH1/Sur and Mixer/Bon can account for all Nodal signaling during embryogenesis. We find that sur expression is independent of Nodal signaling and that bon is expressed in the absence of Nodal signaling but requires Nodal signaling and Sur for enhanced, maintained expression. These results and the association of FoxH1 and Mixer/Bon with phosphorylated Smad2 support a role for these factors as components of the Nodal signaling pathway. In contrast to the relatively mild defects observed in single mutants, loss of both bon and sur results in a severe phenotype characterized by absence of prechordal plate, cardiac mesoderm, endoderm and ventral neuroectoderm. Analysis of Nodal-regulated proteins reveals that Bon and Sur have both distinct and overlapping regulatory roles. Some genes are regulated by both Bon and Sur, and others by either Bon or Sur. Complete loss of Nodal signaling results in a more severe phenotype than loss of both Bon and Sur, indicating that additional Smad-associated transcription factors remain to be identified that act as components of the Nodal signaling pathway.
Genes / Markers
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Human Disease / Model
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Mapping