The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo

• DOI: 10.1101/gad.12.1.107
• Publication Date: 2008-02-20T22:15:26Z
• Authors: Christian Sirard; José Luis de la P...; Andrew Elia; Annick Itie; Christine Mirtsos; Alison Cheung; Stephan Hahn; Andrew Wakeham; Lois Schwartz; Scott E. Kern; Janet Rossant; Tak W. Mak
• Keywords: Epiblast; Brachyury

Mutations in the SMAD4/DPC4 tumor suppressor gene, a key signal transducer most TGFβ-related pathways, are involved 50% of pancreatic cancers. Homozygous Smad4 mutant mice die before day 7.5 embryogenesis. Mutant embryos have reduced size, fail to gastrulate or express mesodermal marker, and show abnormal visceral endoderm development. Growth retardation -deficient results from cell proliferation rather than increased apoptosis. Aggregation ES cells with wild-type tetraploid morulae rescues gastrulation defect. These indicate that is initially required for differentiation defect epiblast secondary non-cell autonomous. Rescued severe anterior truncations, indicating second important role patterning during