Essential Requirement of CCAAT/Enhancer Binding Proteins in Embryogenesis

Abstract

The CCAAT/enhancer binding proteins C/EBPalpha and C/EBPbeta are related transcription factors that are important for the function of various organs in the postnatal mouse. Gene replacement and tissue culture experiments have suggested partial redundancy of both transcription factors. Here we show that mouse embryos deficient of both C/EBPalpha and C/EBPbeta (C/EBPalphabeta(-/-)) die between embryonic day 10 (E10) and E11 and display defective placentas. In situ hybridization revealed that C/EBPalpha and C/EBPbeta are coexpressed in the chorionic plate at E9.5 and later in the trophoblasts of the labyrinthine layer. In C/EBPalphabeta(-/-) placentas, allantoic blood vessels invaded the chorion; however, vessel expansion and development of the labyrinthine layer was impaired. Furthermore, a single copy of either C/EBPalpha in the absence of C/EBPbeta or C/EBPbeta in the absence of C/EBPalpha is sufficient to complete development, suggesting complementation of these C/EBPs during embryogenesis. A single copy of C/EBPalpha in the absence of C/EBPbeta, however, fails to rescue survival after birth, suggesting haploinsufficiency of C/EBPalpha in newborns. Our data thus reveal novel essential, redundant, and dosage dependent functions of C/EBPs.