The winged helix transcriptional activator HFH-8 is expressed in the mesoderm of the primitive streak stage of mouse embryos and its cellular derivatives
The winged helix transcriptional activator HFH-8 is expressed in the mesoderm of the primitive streak stage of mouse embryos and its cellular derivatives
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DOI：
10.1016/s0925-4773(97)00153-6
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发表时间：
1997-12-01
影响因子：
2.6
通讯作者：
Costa, RH
中科院分区：
文献类型：
--
作者：
Peterson, RS;Lim, L;Costa, RH
肝细胞核因子3/叉头同源物（HFH）蛋白是一个广泛的转录因子家族，它们在翼状螺旋DNA结合结构域中具有同源性。有翼螺旋家族的成员在模式形成、器官发生和细胞类型特异性基因表达过程中参与细胞命运的决定。在这项研究中，我们使用原位杂交，以确定在小鼠胚胎发育过程中的细胞表达模式的翅螺旋转录因子，HFH-8。我们发现，HFH-8的表达启动在原条阶段的小鼠胚胎发生的胚外中胚层和侧中胚层，从而产生体侧和内脏侧中胚层。在器官发生过程中，HFH-8的表达被发现在内脏中胚层中的肠内胚层的紧密贴壁，这表明在肺和肠形态发生的间充质-上皮诱导的作用。HFH-8表达在整个小鼠发育过程中持续存在于侧向中胚层来源的组织中。在口腔、食管、气管、肺、肠、背主动脉和体间动脉的间充质细胞中观察到HFH-8表达，但在头部、肝脏、肾脏或心脏的脉管系统中未观察到。与这些胚胎表达研究一致，成人HFH-8表达限于肺泡囊的内皮和结缔成纤维细胞以及肠的固有层和平滑肌。我们还表明，几个成人内皮细胞系保持丰富的HFH-8表达。此外，我们使用我们确定的HFH-8共有序列来鉴定肺和肠间充质细胞中表达的推定靶基因。与这些目标启动子之一，P-选择素，共转染试验表明，HFH-8的表达是必需的IL-6刺激P-选择素启动子活性，并表明HFH-8参与介导其细胞特异性转录激活响应细胞因子。(C)1997 Elsevier Science爱尔兰有限公司
The hepatocyte nuclear factor 3/fork head homolog (HFH) proteins are an extensive family of transcription factors which share homology in the winged helix DNA binding domain. Members of the winged helix family have been implicated in cell fate determination during pattern formation, in organogenesis and in cell type-specific gene expression. In this study, we used in situ hybridization to identify the cellular expression pattern of the winged helix transcription factor, HFH-8, during mouse embryonic development. We showed that HFH-8 expression initiates during the primitive streak stage of mouse embryogenesis in the extraembryonic mesoderm and in the lateral mesoderm which gives rise to the somatopleuric and splanchnopleuric mesoderm. During organogenesis, HFH-8 expression is found in the splanchnic mesoderm in close apposition of the gut endoderm, suggesting a role in mesenchymal-epithelial induction of lung and gut morphogenesis. HFH-8 expression continues in lateral mesoderm-derived tissue throughout mouse development. HFH-8 expression is observed in the mesenchymal cells of the oral cavity, esophagus, trachea, lung, intestine, dorsal aorta and intersomitic arteries, but not in the vasculature of the head, liver, kidney or heart. Consistent with these embryonic expression studies, adult HFH-8 expression is restricted to the endothelium and connective fibroblasts of the alveolar sac and in the lamina propria and smooth muscle of the intestine. We also show that several adult endothelial cell lines maintain abundant HFH-8 expression. Furthermore, we used our determined HFH-8 consensus sequence to identify putative target genes expressed in pulmonary and intestinal mesenchymal cells. Cotransfection assays with one of these target promoters, P-selectin, demonstrated that HFH-8 expression was required for IL-6 stimulation of P-selectin promoter activity and suggest that HFH-8 is involved in mediating its cell-specific transcriptional activation in response to cytokines. (C) 1997 Elsevier Science Ireland Ltd.