Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos. Genes Dev 1994 Oct 15;8(20):2466-77
Date
10/15/1994Pubmed ID
7958910DOI
10.1101/gad.8.20.2466Scopus ID
2-s2.0-0028148776 (requires institutional sign-in at Scopus site) 509 CitationsAbstract
Expression of HNF-4, a transcription factor in the steroid hormone receptor superfamily, is detected only in the visceral endoderm of mouse embryos during gastrulation and is expressed in certain embryonic tissues from 8.5 days of gestation. To examine the role of HNF-4 during embryonic development, we disrupted the gene in embryonic stem cells and found that the homozygous loss of functional HNF-4 protein was an embryonic lethal. Cell death was evident in the embryonic ectoderm at 6.5 days when these cells normally initiate gastrulation. As assessed by expression of Brachyury and HNF-3 beta, primitive streak formation and initial differentiation of mesoderm do occur, but with a delay of approximately 24 h. Development of embryonic structures is severely impaired. These results demonstrate that the expression of HNF-4 in the visceral endoderm is essential for embryonic ectoderm survival and normal gastrulation.
Author List
Chen WS, Manova K, Weinstein DC, Duncan SA, Plump AS, Prezioso VR, Bachvarova RF, Darnell JE JrMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Cell Death
DNA Primers
DNA-Binding Proteins
Embryonic and Fetal Development
Endocytosis
Endoderm
Female
Gastrula
Gene Expression Regulation, Developmental
Genetic Markers
Hepatocyte Nuclear Factor 4
Homozygote
Male
Mesoderm
Mice
Mice, Mutant Strains
Molecular Sequence Data
Phosphoproteins
Transcription Factors
