Morphogenesis of the trachea and esophagus: current players and new roles for noggin and Bmps
Morphogenesis of the trachea and esophagus: current players and new roles for noggin and Bmps
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DOI：
10.1111/j.1432-0436.2006.00096.x
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发表时间：
2006-09-01
期刊：
影响因子：
2.9
通讯作者：
Hogan, Brigid L. M.
中科院分区：
文献类型：
--
作者：
Que, Jianwen;Choi, Murim;Hogan, Brigid L. M.
哺乳动物胚胎前前肠的发育涉及上皮内胚层和相邻中胚层行为的变化。发生的形态发生过程包括中线脊索细胞从上皮定形内胚层中挤出，内胚层折叠成前肠管，以及随后前肠管分离成气管和食管。前肠形态发生缺陷是人类出生缺陷的基础，称为食管闭锁（EA）和气管食管瘘（TEF）。在这里，我们回顾什么是已知的细胞事件在前肠形态发生和基因突变与EA和TEF在小鼠和人类。我们提出了新的证据表明，约70%的小鼠胚胎纯合子无效的Nog，基因编码的头蛋白，骨形态发生蛋白（BMP）拮抗剂，有EA/TEF以及缺陷，在肺分支。这种表型似乎与脊索的异常形态发生及其与定形内胚层分离的缺陷相关。Nog无效突变体的前肠和肺形态发生的异常可以通过将Bmp4的基因剂量减少50%来挽救。这表明正常的前肠形态发生需要Bmp4活性水平通过拮抗剂如noggin小心控制。Bmps正常发挥作用的机制有几种，包括调节脊索和前肠内胚层细胞的细胞间粘附和行为。未来的研究必须确定Noggin/Bmp拮抗作用如何适应已知调节小鼠或人类气管和食管发育的其他因素的网络。
The development of the anterior foregut of the mammalian embryo involves changes in the behavior of both the epithelial endoderm and the adjacent mesoderm. Morphogenetic processes that occur include the extrusion of midline notochord cells from the epithelial definitive endoderm, the folding of the endoderm into a foregut tube, and the subsequent separation of the foregut tube into trachea and esophagus. Defects in foregut morphogenesis underlie the constellation of human birth defects known as esophageal atresia (EA) and tracheoesophageal fistula (TEF). Here, we review what is known about the cellular events in foregut morphogenesis and the gene mutations associated with EA and TEF in mice and humans. We present new evidence that about 70% of mouse embryos homozygous null for Nog, the gene encoding noggin, a bone morphogenetic protein (Bmp) antagonist, have EA/TEF as well as defects in lung branching. This phenotype appears to correlate with abnormal morphogenesis of the notochord and defects in its separation from the definitive endoderm. The abnormalities in foregut and lung morphogenesis of Nog null mutant can be rescued by reducing the gene dose of Bmp4 by 50%. This suggests that normal foregut morphogenesis requires that the level of Bmp4 activity is carefully controlled by means of antagonists such as noggin. Several mechanisms are suggested for how Bmps normally function, including by regulating the intercellular adhesion and behavior of notochord and foregut endoderm cells. Future research must determine how Noggin/Bmp antagonism fits into the network of other factors known to regulate tracheal and esophagus development, both in mouse or humans.