Aamar Emil, Frank Dale
Department of Biochemistry, The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Development. 2004 Jan;131(1):153-63. doi: 10.1242/dev.00905. Epub 2003 Dec 3.
Knockdown studies in Xenopus demonstrated that the XMeis3 gene is required for proper hindbrain formation. An explant assay was developed to distinguish between autonomous and inductive activities of XMeis3 protein. Animal cap explants caudalized by XMeis3 were recombined with explants neuralized by the BMP dominant-negative receptor protein. XMeis3-expressing cells induced convergent extension cell elongations in juxtaposed neuralized explants. Elongated explants expressed hindbrain and primary neuron markers, and anterior neural marker expression was extinguished. Cell elongation was dependent on FGF/MAP-kinase and Wnt-PCP activities. XMeis3 activates FGF/MAP-kinase signaling, which then modulates the PCP pathway. In this manner, XMeis3 protein establishes a hindbrain-inducing center that determines anteroposterior patterning in the brain.
在非洲爪蟾中的敲低研究表明,XMeis3基因是正常后脑形成所必需的。开发了一种外植体分析方法来区分XMeis3蛋白的自主活性和诱导活性。用XMeis3使尾化的动物帽外植体与用BMP显性负性受体蛋白神经化的外植体重组。表达XMeis3的细胞在并列的神经化外植体中诱导细胞伸长和汇聚延伸。伸长的外植体表达后脑和初级神经元标记物,并且前神经标记物的表达消失。细胞伸长依赖于FGF/丝裂原活化蛋白激酶(MAP-激酶)和Wnt-平面细胞极性(PCP)活性。XMeis3激活FGF/MAP-激酶信号传导,然后调节PCP途径。通过这种方式,XMeis3蛋白建立了一个后脑诱导中心,该中心决定了大脑中的前后模式。