Open AccessPostgastrulation Smad2- deficient embryos show defects in embryo turning and anterior morphogenesis
Author(s) -
Joerg Heyer,
Diana EscalanteAlcalde,
Marie Lia,
Erwin Boettinger,
Winfried Edelmann,
Colin L. Stewart,
Raju Kucherlapati
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.22.12595
Subject(s) - embryo , morphogenesis , biology , embryology , microbiology and biotechnology , anatomy , genetics , gene
SMAD2 is a member of the transforming growth factor β and activin-signaling pathway. To examine the role ofSmad2 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 geneHex (the earliest known marker of the A-P polarity and the prospective head organizer) was found to be missing inSmad2- 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 thatSmad2 expression is required at several stages during embryogenesis.