Maatouk Danielle M, Choi Kyung-Suk, Bouldin Cortney M, Harfe Brian D
Department of Molecular Genetics and Microbiology and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL 32611, USA.
Dev Biol. 2009 Mar 15;327(2):516-23. doi: 10.1016/j.ydbio.2009.01.004. Epub 2009 Jan 13.
The apical ectodermal ridge (AER) in the vertebrate limb is required for limb outgrowth and patterning. To investigate the role BMP ligands expressed in the AER play in limb development we selectively inactivated both Bmp2 and Bmp4 in this tissue. The autopods of mice lacking both of these genes contained extra digits, digit bifurcations and interdigital webbing due to a decrease in programmed cell death and an increase in cell proliferation in the underlying mesoderm. Upon removal of Bmp2 and Bmp4 in the AER, no defects in proximal-distal patterning were observed. At the molecular level, removal of Bmp2 and Bmp4 in the AER caused an increase in Fgf expression, which correlated with an increase in both the width and length of the AER. Investigation of Engrailed-1 (En1) expression in the AER of limb buds in which Bmp2 and Bmp4 had been removed indicated that En1 expression was absent from this tissue. Our data suggests that AER expression of Bmp2 and Bmp4 is required for digit and dorsal-ventral patterning but surprisingly not for limb outgrowth.
脊椎动物肢体中的顶端外胚层嵴（AER）对于肢体的生长和模式形成是必需的。为了研究在AER中表达的BMP配体在肢体发育中的作用，我们在该组织中选择性地使Bmp2和Bmp4失活。缺乏这两个基因的小鼠的 autopods 由于其下方中胚层中程序性细胞死亡减少和细胞增殖增加而出现额外的指（趾）、指（趾）分叉和指间蹼。在AER中去除Bmp2和Bmp4后，未观察到近端 - 远端模式形成的缺陷。在分子水平上，在AER中去除Bmp2和Bmp4导致Fgf表达增加，这与AER的宽度和长度增加相关。对已去除Bmp2和Bmp4的肢体芽的AER中Engrailed-1（En1）表达的研究表明，该组织中不存在En1表达。我们的数据表明，Bmp2和Bmp4在AER中的表达对于指（趾）和背 - 腹模式形成是必需的，但令人惊讶的是对于肢体生长不是必需的。
