C-Fos elimination compensates for disabled-2 requirement in mouse extraembryonic endoderm development.

Disabled-2 (Dab2) is expressed in primitive endoderm cells as they are differentiating from the inner cell mass and dab2 deficiency in mice results in lethality at E5.5-E6.5 due to the disorganization of the endoderm layers. Here we show that Dab2 suppresses c-Fos expression in endoderm cells. A morphological normal primitive endoderm layer was observed in putative E5.5 dab2 (-/-):c-fos (-/-) embryos, indicating that the primitive endoderm defect due to the loss of Dab2 is rescued by deletion of the c-fos gene. The lethality of the double knockout embryos was delayed until E9.5-E10.5 and the defective embryos failed to undergo organogenesis. We conclude that Dab2 plays a role in epithelial organization by suppression of c-Fos expression and suggest that unsuppressed c-Fos can lead to disruption of primitive endoderm epithelial organization, yet an additional dab2 function is required for later organogenesis. (c) 2009 Wiley-Liss, Inc.