Epiblast-specific loss of HCF-1 leads to failure in anterior-posterior axis specification

Dev Biol. 2016 Oct 1;418(1):75-88. doi: 10.1016/j.ydbio.2016.08.008. Epub 2016 Aug 9.

Abstract

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 β-catenin function. These results reveal essential new roles for HCF-1 in early embryonic cell proliferation and development.

Keywords: AVE; Cell cycle; Embryonic lethality; Gastrulation; HCF-1/Hcfc1; Primitive streak.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Cell Cycle / genetics
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Embryonic Development / genetics*
  • Endoderm / cytology
  • Endoderm / metabolism
  • Female
  • Gastrulation / genetics
  • Gene Expression Regulation, Developmental
  • Genes, X-Linked / genetics
  • Host Cell Factor C1 / genetics*
  • In Situ Nick-End Labeling
  • Male
  • Mice
  • Mice, Knockout
  • Signal Transduction
  • beta Catenin / metabolism

Substances

  • Hcfc1 protein, mouse
  • Host Cell Factor C1
  • beta Catenin