Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Development. 2011 Nov;138(21):4743-52. doi: 10.1242/dev.066548. Epub 2011 Sep 28.
How organ size and form are controlled during development is a major question in biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here, we report that, surprisingly, non-nutritional signals from blood vessels act to restrain pancreas growth. Elimination of endothelial cells increases the size of embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases pancreas size. The growth phenotype results from vascular restriction of pancreatic tip cell formation, lateral branching and differentiation of the pancreatic epithelium into endocrine and acinar cells. The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus, the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells.
器官的大小和形态如何在发育过程中得到控制，是生物学中的一个重大问题。已有研究表明，血管对于肝脏和胰腺的早期发育至关重要，并且是正常和病理组织生长的基础。在这里，我们报告了一个令人惊讶的发现，即血管的非营养信号出人意料地起到了抑制胰腺生长的作用。内皮细胞的消除会增加胚胎胰腺芽的大小。相反，VEGF 诱导的过度血管生成会减小胰腺的大小。生长表型是由于血管限制了胰腺顶端细胞的形成、胰腺上皮细胞的侧支分支以及向内分泌细胞和腺泡细胞的分化。这种作用在体内和体外都能观察到，表明这是一种与灌注无关的机制。因此，血管通过减少原始上皮细胞的分支和分化来控制胰腺形态发生和生长。
