Amaya E, Stein P A, Musci T J, Kirschner M W
Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
Development. 1993 Jun;118(2):477-87. doi: 10.1242/dev.118.2.477.
We have examined the role of FGF signalling in the development of muscle and notochord and in the expression of early mesodermal markers in Xenopus embryos. Disruption of the FGF signalling pathway by expression of a dominant negative construct of the FGF receptor (XFD) generally results in gastrulation defects that are later evident in the formation of the trunk and tail, though head structures are formed nearly normally. These defects are reflected in the loss of notochord and muscle. Even in embryos that show mild defects and gastrulate properly, muscle formation is impaired, suggesting that morphogenesis and tissue differentiation each depend on FGF. The XFD protein inhibits the expression of the immediate early gene brachyury throughout the marginal zone, including the dorsal side; it does not, however, inhibit the dorsal lip marker goosecoid, which is expressed in the first involuting mesoderm at the dorsal side that will underlie the head. The XFD protein also inhibits Xpo expression, an immediate early marker of ventral and lateral mesoderm. These results suggest that FGF is involved in the earliest events of most mesoderm induction that occur before gastrulation and that the early dorsal mesoderm is already composed of two cell populations that differ in their requirements for FGF.
我们研究了成纤维细胞生长因子(FGF)信号通路在非洲爪蟾胚胎肌肉和脊索发育以及早期中胚层标志物表达中的作用。通过表达FGF受体(XFD)的显性负性构建体来破坏FGF信号通路,通常会导致原肠胚形成缺陷,这种缺陷随后在躯干和尾部的形成中明显表现出来,尽管头部结构几乎正常形成。这些缺陷表现为脊索和肌肉的缺失。即使在显示轻度缺陷且原肠胚形成正常的胚胎中,肌肉形成也会受损,这表明形态发生和组织分化均依赖于FGF。XFD蛋白在整个边缘区(包括背侧)抑制即刻早期基因短尾相关蛋白(brachyury)的表达;然而,它并不抑制背侧唇标记物鹅膏蕈氨酸结合蛋白(goosecoid)的表达,该蛋白在背侧最早内卷的中胚层中表达,此中胚层将构成头部的基础。XFD蛋白还抑制Xpo的表达,Xpo是腹侧和外侧中胚层的即刻早期标志物。这些结果表明,FGF参与了原肠胚形成之前大多数中胚层诱导的最早事件,并且早期背侧中胚层已经由两个对FGF需求不同的细胞群体组成。