کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5531998 1401825 2016 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Epiblast-specific loss of HCF-1 leads to failure in anterior-posterior axis specification
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Epiblast-specific loss of HCF-1 leads to failure in anterior-posterior axis specification
چکیده انگلیسی


- Epiblast-specific HCF-1 depletion leads to developmental arrest by E6.5.
- HCF-1-deficient cells rapidly exit the cell cycle.
- Epiblast-specific HCF-1 depletion impairs A-P axis specification and gastrulation.
- Loss of HCF-1 affects β-catenin activation.
- Loss of HCF-1 in the epiblast phenocopies embryonic loss of β-catenin.

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 Hcfc1cKO/+ 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, Hcfc1epiKO/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 Hcfc1epiKO/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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Developmental Biology - Volume 418, Issue 1, 1 October 2016, Pages 75-88
نویسندگان
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