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Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis

  1. Author:
    Heyer, J.
    Escalante-Alcalde, D.
    Lia, M.
    Boettinger, E.
    Edelmann, W.
    Stewart, C. L.
    Kucherlapati, R.

  2. Author Address

    Kucherlapati R Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet 1300 Morris Pk Ave Bronx, NY 10461 USA Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet Bronx, NY 10461 USA Yeshiva Univ Albert Einstein Coll Med, Dept Med Bronx, NY 10461 USA Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol Bronx, NY 10461 USA NCI, Frederick Canc Res & Dev Ctr, Basic Res Program, Adv BioSci Lab,Canc & Dev Biol Lab Frederick, MD 21702 USA
    1. Year: 1999
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 96
    2. 22
    3. Pages: 12595-12600
  4. Type of Article: Article
  1. Abstract:

    SMAD2 is a member of the transforming growth factor beta and activin-signaling pathway, To examine the role of Smad2 in postgastrulation development, we independently generated mice with a null mutation in this gene. Smad2-deficient embryos die around day 7.5 of gestation because of failure of gastrulation and failure to establish an anterior-posterior (A-P) axis. Expression of the homeobox gene Hex (the earliest known marker of the A-P polarity and the prospective head organizer) was found to be missing in Smad2-deficient embryos. Homozygous mutant embryos and embryonic stem cells formed mesoderm derivatives revealing that mesoderm induction is SMAD2 independent. In the presence of wild-type extraembryonic tissues, Smad2-deficient embryos developed beyond 7.5 and up to 10.5 days postcoitum, demonstrating a requirement for SMAD2 in extraembryonic tissues for the generation of an A-P axis and gastrulation, The rescued postgastrulation embryos showed malformation of head structures, abnormal embryo turning, and cyclopia. Our results show that Smad2 expression is required at several stages during embryogenesis. [References: 47]

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