Division of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, 45th Street and Penn Avenue, Pittsburgh, PA 15201, USA.
Dev Biol. 2011 Jan 15;349(2):342-9. doi: 10.1016/j.ydbio.2010.10.033. Epub 2010 Nov 2.
The mammalian embryo represents a fundamental paradox in biology. Its location within the uterus, especially early during development when embryonic cardiovascular development and placental blood flow are not well-established, leads to an obligate hypoxic environment. Despite this hypoxia, the embryonic cells are able to undergo remarkable growth, morphogenesis, and differentiation. Recent evidence suggests that embryonic organ differentiation, including pancreatic β-cells, is tightly regulated by oxygen levels. Since a major determinant of oxygen tension in mammalian embryos after implantation is embryonic blood flow, here we used a novel survivable in utero intracardiac injection technique to deliver a vascular tracer to living mouse embryos. Once injected, the embryonic heart could be visualized to continue contracting normally, thereby distributing the tracer specifically only to those regions where embryonic blood was flowing. We found that the embryonic pancreas early in development shows a remarkable paucity of blood flow and that the presence of blood flow correlates with the differentiation state of the developing pancreatic epithelial cells in the region of the blood flow.
哺乳动物胚胎在生物学上代表了一个基本悖论。它位于子宫内，尤其是在胚胎心血管发育和胎盘血流尚未完全建立的早期，导致胚胎处于必需的低氧环境中。尽管存在这种缺氧，胚胎细胞仍能够进行显著的生长、形态发生和分化。最近的证据表明，胚胎器官分化，包括胰腺β细胞，受到氧水平的严格调控。由于植入后哺乳动物胚胎中氧张力的主要决定因素是胚胎血流，因此我们使用了一种新的可存活的宫内心内注射技术，将血管示踪剂递送至活体小鼠胚胎。一旦注射，胚胎心脏可以继续正常收缩，从而将示踪剂专门分配到胚胎血流所在的区域。我们发现，在发育早期，胚胎胰腺的血流明显减少，而血流的存在与该区域发育中的胰腺上皮细胞的分化状态相关。
