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ZFIN ID: ZDB-PUB-071125-22
smad2 and smad3 Are Required for Mesendoderm Induction by Transforming Growth Factor-β/Nodal Signals in Zebrafish
Jia, S., Ren, Z., Li, X., Zheng, Y., and Meng, A.
Date: 2008
Source: The Journal of biological chemistry   283(4): 2418-2426 (Journal)
Registered Authors: Jia, Shunji, Li, Xiang, Meng, Anming
Keywords: none
MeSH Terms:
  • Activins/genetics
  • Activins/metabolism
  • Amino Acid Substitution
  • Animals
  • Animals, Genetically Modified/embryology
  • Animals, Genetically Modified/genetics
  • Body Patterning/physiology
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental/physiology*
  • Genes, Dominant/genetics
  • Mesoderm/embryology*
  • Nodal Protein
  • Signal Transduction/physiology
  • Smad2 Protein/genetics
  • Smad2 Protein/metabolism*
  • Smad3 Protein/genetics
  • Smad3 Protein/metabolism*
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 18025082 Full text @ J. Biol. Chem.
The TGF-beta ligands Nodal, Activin, and Vg1 play important roles in mesendoderm induction and patterning during vertebrate embryogenesis. These ligands are believed to transduce the signal through the receptor-activated transcription factors Smad2 and Smad3. However, the roles of smad2/3 genes in development of zebrafish embryos are largely unknown, because the presence of multiple smad2/3 genes and their maternal expression has hampered the investigation of their developmental roles. We generated potent and specific dominant negative forms (dn) of zebrafish Smad2, Smad3a, and Smad3b by mutating multiple amino acids. Overexpression of these mutants abolished mesendoderm induction by ectopic Nodal signaling in zebrafish embryos. Expression of dnsmad2/3 abrogated Smad2/3 activities in wildtype embryos and caused various mesendodermal defects similar to Nodal-deficient embryos. Smad2/3-deficient cells transplanted into blastodermal margin of wildtype hosts preferentially differentiate into ectodermal tissues rather than mesendodermal tissues, supporting the idea that response of cells to mesendoderm inducers requires Smad2/3 activities. Interference with Smad2/3 activities in Zoep, Moep and MZoep mutant embryos resulted in more severe mesendodermal defects. Thus, our data reveal that Nodal signaling and mesendoderm induction depend on Smad2/3, and suggest that TGF-beta signals other than Nodal also contribute to Smad2/3 signaling and embryonic patterning.