Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo.
Critical to our understanding of the developmental potential of stem cells and subsequent control of their differentiation in vitro and in vivo is a thorough understanding of the genes that control stem cell fate. Here, we report that Foxd3, a member of the forkhead family of transcriptional regulators, is required for maintenance of embryonic cells of the early mouse embryo. Foxd3-/- embryos die after implantation at approximately 6.5 days postcoitum with a loss of epiblast cells, expansion of proximal extraembryonic tissues, and a distal, mislocalized anterior organizing center. Moreover, it has not been possible to establish Foxd3-/- ES cell lines or to generate Foxd3-/- teratocarcinomas. Chimera analysis reveals that Foxd3 function is required in the epiblast and that Foxd3-/- embryos can be rescued by a small number of wild-type cells. Foxd3-/- mutant blastocysts appear morphologically normal and express Oct4, Sox2, and Fgf4, but when placed in vitro the inner cell mass initially proliferates and then fails to expand even when Fgf4 is added. These results establish Foxd3 as a factor required for the maintenance of progenitor cells in the mammalian embryo.
Hanna
Lynn A
LA
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6058, USA.
Foreman
Ruth K
RK
Tarasenko
Illya A
IA
Kessler
Daniel S
DS
Labosky
Patricia A
PA
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005260:Female; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000378:metabolism; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D019077:Helix-Turn-Helix Motifs / Q000502:physiology; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008297:Male; D051379:Mice / Q000196:embryology*; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D050814:Octamer Transcription Factor-3; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D017931:DNA Primers; D004268:DNA-Binding Proteins; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D051858:Forkhead Transcription Factors; C101757:Foxd3 protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D005346:Fibroblast Growth Factors