Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis.
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.
Heyer
J
J
Departments of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Escalante-Alcalde
D
D
Lia
M
M
Boettinger
E
E
Edelmann
W
W
Stewart
C L
CL
Kucherlapati
R
R
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005775:Gastrula; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D006321:Heart / Q000196:embryology; D006720:Homozygote; D006801:Humans; D051379:Mice; D009024:Morphogenesis; D010641:Phenotype; D051899:Smad2 Protein; D015534:Trans-Activators / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; C497782:SMAD2 protein, human; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D015534:Trans-Activators