Kumar Maya, Jordan Nathalie, Melton Doug, Grapin-Botton Anne
Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Dev Biol. 2003 Jul 1;259(1):109-22. doi: 10.1016/s0012-1606(03)00183-0.
During embryonic development, organs arise along the gut tube as a series of buds in a stereotyped anterior-posterior (A-P) pattern. Using chick-quail chimeras and in vitro tissue recombination, we studied the interactions governing the induction and maintenance of endodermal organ identify focusing on the pancreas. Though several permissive signals in pancreatic development have been previously identified, here we provide evidence that lateral plate mesoderm sends instructive signals to the endoderm, signals that induce expression of the pancreatic genes Pdx1, p48, Nkx6.1, glucagon, and insulin. Moreover, this instructive signal directs cells to form ectopic insulin-positive islet-like clusters in endoderm that would otherwise form more rostral organs. Once generated, endocrine cells no longer require interaction with mesoderm, but nonendocrine cells continue to require permissive signals from the mesoderm. Stimulation of activin, BMP, or retinoic acid signaling is sufficient to induce Pdx1 expression in endoderm anterior to the pancreas. Lateral plate mesoderm appears to pattern the endoderm in a posterior-dominant fashion as first noted in the patterning of the neural tube at the same embryonic stage. These findings argue for a central role of the mesoderm in coordinating the A-P pattern of all three primary germ layers.
在胚胎发育过程中，器官沿着肠管以一系列芽的形式，按照前后（A-P）模式有规律地出现。利用鸡-鹌鹑嵌合体和体外组织重组技术，我们研究了控制内胚层器官身份诱导和维持的相互作用，重点关注胰腺。虽然之前已经鉴定出胰腺发育中的几种许可信号，但在这里我们提供证据表明侧板中胚层向内胚层发送指令性信号，这些信号诱导胰腺基因Pdx1、p48、Nkx6.1、胰高血糖素和胰岛素的表达。此外，这种指令性信号引导细胞在内胚层中形成异位胰岛素阳性胰岛样簇，否则这些内胚层会形成更靠前的器官。一旦产生，内分泌细胞不再需要与中胚层相互作用，但非内分泌细胞仍然需要中胚层的许可信号。激活素、骨形态发生蛋白（BMP）或视黄酸信号的刺激足以在内胚层胰腺前方诱导Pdx1表达。侧板中胚层似乎以后部主导的方式塑造内胚层，这与在同一胚胎阶段神经管的模式形成中首次发现的情况相同。这些发现表明中胚层在协调所有三个主要胚层的前后模式中起着核心作用。
