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.
Yang
Dong-Hua
DH
Ovarian Cancer Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Smith
Elizabeth R
ER
Cai
Kathy Qi
KQ
Xu
Xiang-Xi
XX
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002454:Cell Differentiation; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004707:Endoderm / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; C478773:Dab2 protein, mouse; D016760:Proto-Oncogene Proteins c-fos