| First Author | Minocha S | Year | 2016 |
| Journal | Dev Biol | Volume | 418 |
| Issue | 1 | Pages | 75-88 |
| PubMed ID | 27521049 | Mgi Jnum | J:236404 |
| Mgi Id | MGI:5806015 | Doi | 10.1016/j.ydbio.2016.08.008 |
| Citation | Minocha S, et al. (2016) Epiblast-specific loss of HCF-1 leads to failure in anterior-posterior axis specification. Dev Biol 418(1):75-88 |
| abstractText | Mammalian Host-Cell Factor 1 (HCF-1), a transcriptional co-regulator, plays important roles during the cell-division cycle in cell culture, embryogenesis as well as adult tissue. In mice, HCF-1 is encoded by the X-chromosome-linked Hcfc1 gene. Induced Hcfc1(cKO/+) heterozygosity with a conditional knockout (cKO) allele in the epiblast of female embryos leads to a mixture of HCF-1-positive and -deficient cells owing to random X-chromosome inactivation. These embryos survive owing to the replacement of all HCF-1-deficient cells by HCF-1-positive cells during E5.5 to E8.5 of development. In contrast, complete epiblast-specific loss of HCF-1 in male embryos, Hcfc1(epiKO/Y), leads to embryonic lethality. Here, we characterize this lethality. We show that male epiblast-specific loss of Hcfc1 leads to a developmental arrest at E6.5 with a rapid progressive cell-cycle exit and an associated failure of anterior visceral endoderm migration and primitive streak formation. Subsequently, gastrulation does not take place. We note that the pattern of Hcfc1(epiKO/Y) lethality displays many similarities to loss of beta-catenin function. These results reveal essential new roles for HCF-1 in early embryonic cell proliferation and development. |
