Homeoprotein hhex-induced conversion of intestinal to ventral pancreatic precursors results in the formation of giant pancreata in Xenopus embryos
Homeoprotein hhex-induced conversion of intestinal to ventral pancreatic precursors results in the formation of giant pancreata in Xenopus embryos
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DOI：
10.1073/pnas.1206547109
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发表时间：
2012-05
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影响因子：
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通讯作者：
Hui Zhao;Dandan Han;I. Dawid;T. Pieler;Yonglong Chen
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文献类型：
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作者：
Hui Zhao;Dandan Han;I. Dawid;T. Pieler;Yonglong Chen
肝和腹胰是从原肠胚内胚层的邻近区域发育而来的。腹胰前体1（VPP 1）是在原肠胚形成期间以与造血表达同源框（HHEX）部分重叠的模式在背内胚层内的细胞群中差异表达的标记基因。在尾芽胚胎中，vpp 1表达特异性地划分两个腹侧胰腺芽，而hhex表达主要限于肝憩室。异位表达一个临界剂量的hhex导致vpp 1阳性结构域大大扩大，随后，形成巨大的腹侧胰腺，通过肠腹侧胰腺前体细胞的转换而化脓。相反，反义吗啉代寡核苷酸介导的hhex敲低导致vpp 1表达下调和腹侧胰腺的特定损失。此外，用地塞米松诱导的hhex-VP 16 GR融合构建体滴定hhex表明，原肠胚形成期间的内源性hhex活性对于腹侧胰腺祖细胞的形成是必不可少的。这些观察结果表明，除了在肝脏发育中的作用外，hhex还在原肠胚形成过程中控制vpp 1阳性内胚层细胞群的特异性，这是腹侧胰腺形成所必需的。
Liver and ventral pancreas develop from neighboring territories within the endoderm of gastrulae. ventral pancreatic precursor 1 (vpp1) is a marker gene that is differentially expressed in a cell population within the dorsal endoderm in a pattern partially overlapping with that of hematopoietically expressed homeobox (hhex) during gastrulation. In tail bud embryos, vpp1 expression specifically demarcates two ventral pancreatic buds, whereas hhex expression is mainly restricted to the liver diverticulum. Ectopic expression of a critical dose of hhex led to a greatly enlarged vpp1-positive domain and, subsequently, to the formation of giant ventral pancreata, putatively by conversion of intestinal to ventral pancreatic precursor cells. Conversely, antisense morpholino oligonucleotide-mediated knockdown of hhex resulted in a down-regulation of vpp1 expression and a specific loss of the ventral pancreas. Furthermore, titration of hhex with a dexamethasone-inducible hhex-VP16GR fusion construct suggested that endogenous hhex activity during gastrulation is essential for the formation of ventral pancreatic progenitor cells. These observations suggest that, beyond its role in liver development, hhex controls specification of a vpp1-positive endodermal cell population during gastrulation that is required for the formation of the ventral pancreas.