Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants

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Abstract

THE identity and patterning of ventral cell types in the vertebrate central nervous system depends on cell interactions1. 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 noto-chord and floor plate can induce ventrolaterally positioned motor neurons. Sonic hedgehog (Shh), a vertebrate hedgehog-family member, is processed to generate two peptides (Mr 19K and 26/27K) which are secreted by both of these organizing centres2,30. Moreover, experiments in a variety of vertebrate embryos3-5, and in neural explants in vitro5, 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 (Mr 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.

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Marti, E., Bumcrot, D., Takada, R. et al. Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants. Nature 375, 322–325 (1995) doi:10.1038/375322a0

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