Reversade Bruno, Kuroda Hiroki, Lee Hojoon, Mays Ashley, De Robertis Edward M
Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, CA 90095-1662, USA.
Development. 2005 Aug;132(15):3381-92. doi: 10.1242/dev.01901. Epub 2005 Jun 23.
To address the patterning function of the Bmp2, Bmp4 and Bmp7 growth factors, we designed antisense morpholino oligomers (MO) that block their activity in Xenopus laevis. Bmp4 knockdown was sufficient to rescue the ventralizing effects caused by loss of Chordin activity. Double Bmp4 and Bmp7 knockdown inhibited tail development. Triple Bmp2/Bmp4/Bmp7 depletion further compromised trunk development but did not eliminate dorsoventral patterning. Unexpectedly, we found that blocking Spemann organizer formation by UV treatment or beta-Catenin depletion caused BMP inhibition to have much more potent effects, abolishing all ventral development and resulting in embryos having radial central nervous system (CNS) structures. Surprisingly, dorsal signaling molecules such as Chordin, Noggin, Xnr6 and Cerberus were not re-expressed in these embryos. We conclude that BMP inhibition is sufficient for neural induction in vivo, and that in the absence of ventral BMPs, Spemann organizer signals are not required for brain formation.
为了研究骨形态发生蛋白2(Bmp2)、骨形态发生蛋白4(Bmp4)和骨形态发生蛋白7(Bmp7)生长因子的模式形成功能,我们设计了反义吗啉代寡聚核苷酸(MO),以阻断它们在非洲爪蟾中的活性。敲低Bmp4足以挽救因脊索蛋白活性丧失而导致的腹侧化效应。同时敲低Bmp4和Bmp7会抑制尾部发育。三重敲低Bmp2/Bmp4/Bmp7会进一步损害躯干发育,但不会消除背腹模式形成。出乎意料的是,我们发现通过紫外线处理或β-连环蛋白敲低来阻断施佩曼组织者的形成,会使BMP抑制产生更强的效果,消除所有腹侧发育,并导致胚胎具有放射状中枢神经系统(CNS)结构。令人惊讶的是,在这些胚胎中,诸如脊索蛋白、头蛋白、Xnr6和Cerberus等背侧信号分子并未重新表达。我们得出结论,在体内BMP抑制足以诱导神经形成,并且在没有腹侧BMP的情况下,大脑形成不需要施佩曼组织者信号。