Transcriptional regulator BPTF/FAC1 is essential for trophoblast differentiation during early mouse development.
The putative transcriptional regulator BPTF/FAC1 is expressed in embryonic and extraembryonic tissues of the early mouse conceptus. The extraembryonic trophoblast lineage in mammals is essential to form the fetal part of the placenta and hence for the growth and viability of the embryo in utero. Here, we describe a loss-of-function allele of the BPTF/FAC1 gene that causes embryonic lethality in the mouse. BPTF/FAC1-deficient embryos form apparently normal blastocysts that implant and develop epiblast, visceral endoderm, and extraembryonic ectoderm including trophoblast stem cells. Subsequent development of mutants, however, is arrested at the early gastrula stage (embryonic day 6.5), and virtually all null embryos die before midgestation. Most notably, the ectoplacental cone is drastically reduced or absent in mutants, which may cause the embryonic lethality. Development of the mutant epiblast is also affected, as the anterior visceral endoderm and the primitive streak do not form correctly, while brachyury-expressing mesodermal cells arise but are delayed. The mutant phenotype suggests that gastrulation is initiated, but no complete anteroposterior axis of the epiblast appears. We conclude that BPTF/FAC1 is essential in the extraembryonic lineage for correct development of the ectoplacental cone and fetomaternal interactions. In addition, BPTF/FAC1 may also play a role either directly or indirectly in anterior-posterior patterning of the epiblast.
Goller
Tobias
T
Cell and Molecular Biology, University of Braunschweig, Spielmann Str. 7, 38106 Braunschweig, Germany.
Vauti
Franz
F
Ramasamy
Suresh
S
Arnold
Hans-Henning
HH
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D016207:Cytokines; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology*; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*; D000098908:Brachyury Protein; D000092468:Bromodomain Containing Proteins
D034961:Antigens, Nuclear; D015415:Biomarkers; D016207:Cytokines; D005326:Fetal Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein; C110586:Cer1 protein, mouse; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins
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