An endothelial-mesenchymal relay pathway regulates early phases of pancreas development
An endothelial-mesenchymal relay pathway regulates early phases of pancreas development
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DOI：
10.1016/j.ydbio.2005.11.023
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发表时间：
2006-02-01
影响因子：
2.7
通讯作者：
Zaret, KS
中科院分区：
文献类型：
--
作者：
Jacquemin, P;Yoshitomi, H;Zaret, KS
了解从胚胎内胚层诱导胰腺祖细胞的组织相互作用，可以深入了解先天性畸形、组织修复以及将干细胞分化为胰腺命运。背侧内胚层上皮内胰腺祖细胞的特化被认为涉及中胚层相互作用的两个阶段；首先是侧板中胚层和脊索，然后是主动脉内皮细胞。随后，胰芽的分支形态发生由 Isl-1 阳性背侧间充质细胞诱导，其生长受到循环中因子的刺激。使用小鼠遗传模型和胚胎组织外植体，我们表明主动脉内皮和背侧间充质在分支形态发生步骤之前在胰腺诱导中均具有额外的作用。具体来说，我们发现主动脉内皮细胞促进附近 Isl-1 阳性背侧间质的存活，与循环因素无关。此外，我们发现来自间充质细胞的 FGF10 信号传导维持了背侧胰芽中 Ptf1a 的表达，并且在转录因子基因 HNF6 促进 Pdx-1 阳性背侧内胚层诱导中的作用似乎具有遗传冗余。总之，这些研究揭示了从主动脉内皮到背侧间质再到内胚层的中继途径，以及背侧间质在器官形态发生之前促进背侧胰腺内胚层初始分化的功能。 (c) 2005 Elsevier Inc. 保留所有权利。
Understanding the tissue interactions that induce pancreatic progenitor cells from the embryonic endoderm provides insights into congenital malformations, tissue repair, and differentiating stem cells to a pancreatic fate. The specification of pancreatic progenitors within the dorsal endodermal epithelium has been thought to involve two phases of mesodermal interactions; first with the lateral plate mesoderm and notochord and then with aortic endothelial cells. Afterwards, branching morphogenesis of the pancreatic bud is induced by Isl-1-positive dorsal mesenchyme cells, whose growth is stimulated by factors in the circulation. Using mouse genetic models and embryo tissue explants, we show that the aortic endothelium and dorsal mesenchyme each possess an additional role in pancreatic induction, prior to the branching morphogenesis step. Specifically, we find that aortic endothelial cells promote the survival of nearby, Isl-1-positive dorsal mesenchyme, independently of factors from the circulation. Furthermore, we find that FGF10 signaling from the mesenchyme cells maintains Ptf1a expression in the dorsal pancreatic bud and appears genetically redundant with a role for the transcription factor gene HNF6 in promoting the induction of Pdx-1-positive dorsal endoderm. Together, these Studies reveal a relay pathway from aortic endothelium to dorsal mesenchyme and then to the endoderm, along with functions of the dorsal mesenchyme that promote the initial differentiation of the dorsal pancreatic endoderm, prior to organ morphogenesis. (c) 2005 Elsevier Inc. All rights reserved.