Martí E, Bumcrot D A, Takada R, McMahon A P
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature. 1995 May 25;375(6529):322-5. doi: 10.1038/375322a0.
The identity and patterning of ventral cell types in the vertebrate central nervous system depends on cell interactions. For example, induction of a specialized population of ventral midline cells, the floor plate, appears to require contact-mediated signalling by the underlying notochord, whereas diffusible signals from the notochord and floor plate can induce ventrolaterally positioned motor neurons. Sonic hedgehog (Shh), a vertebrate hedgehog-family member, is processed to generate two peptides (M(r) 19K and 26/27K) which are secreted by both of these organizing centres. Moreover, experiments in a variety of vertebrate embryos, and in neural explants in vitro, indicate that Shh can mediate floor-plate induction. Here we have applied recombinant Shh peptides to neural explants in serum-free conditions. High concentrations of Shh bound to a matrix induce floor plate and motor neurons, and addition of Shh to the medium leads to dose-dependent induction of motor neurons. All inducing activity resides in a highly conserved amino-terminal peptide (M(r) 19K). Moreover, antibodies that specifically recognize this peptide block induction of motor neurons by the notochord. We propose that Shh acts as a morphogen to induce distinct ventral cell types in the vertebrate central nervous system.
脊椎动物中枢神经系统中腹侧细胞类型的特性及模式形成依赖于细胞间的相互作用。例如，诱导腹侧中线细胞的一个特化群体——底板，似乎需要其下方脊索通过接触介导的信号传导，而来自脊索和底板的可扩散信号能够诱导腹外侧定位的运动神经元。音猬因子（Shh）是脊椎动物刺猬家族的成员，它被加工产生两种肽（分子量分别为19K和26/27K），这两个组织中心均可分泌这两种肽。此外，在多种脊椎动物胚胎以及体外神经外植体中所做的实验表明，Shh能够介导底板的诱导。在此，我们将重组Shh肽应用于无血清条件下的神经外植体。与基质结合的高浓度Shh可诱导底板和运动神经元的产生，向培养基中添加Shh会导致运动神经元的剂量依赖性诱导。所有诱导活性都存在于一个高度保守的氨基末端肽（分子量19K）中。此外，特异性识别该肽的抗体可阻断脊索对运动神经元的诱导。我们认为，Shh作为一种形态发生素，在脊椎动物中枢神经系统中诱导不同的腹侧细胞类型。
