DISRUPTION OF THE HNF-4 GENE, EXPRESSED IN VISCERAL ENDODERM, LEADS TO CELL-DEATH IN EMBRYONIC ECTODERM AND IMPAIRED GASTRULATION OF MOUSE EMBRYOS
DISRUPTION OF THE HNF-4 GENE, EXPRESSED IN VISCERAL ENDODERM, LEADS TO CELL-DEATH IN EMBRYONIC ECTODERM AND IMPAIRED GASTRULATION OF MOUSE EMBRYOS
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DOI：
10.1101/gad.8.20.2466
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发表时间：
1994-10-15
影响因子：
10.5
通讯作者：
DARNELL, JE
中科院分区：
文献类型：
--
作者：
CHEN, WS;MANOVA, K;DARNELL, JE
类固醇激素受体超家族中的转录因子HNF-4的表达仅在原肠胚形成期间小鼠胚胎的内脏内胚层中检测到，并且从妊娠8.5天开始在某些胚胎组织中表达。为了研究HNF-4在胚胎发育过程中的作用，我们破坏了胚胎干细胞中的基因，发现功能性HNF-4蛋白的纯合丢失是胚胎致死的。细胞死亡是明显的胚胎外胚层在6.5天时，这些细胞通常启动原肠胚。如通过Brachyury和HNF-3 β的表达所评估的，原始条纹形成和中胚层的初始分化确实发生，但是具有类似于24小时的延迟。胚胎结构的发育严重受损。这些结果表明，内脏内胚层中HNF-4的表达是胚胎外胚层存活和正常原肠胚形成所必需的。
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 similar to 24 hr. 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.