title: Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: E
authors.initials: E
authors.lastname: Martí
authors.forename: D A
authors.initials: DA
authors.lastname: Bumcrot
authors.forename: R
authors.initials: R
authors.lastname: Takada
authors.forename: A P
authors.initials: AP
authors.lastname: McMahon
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001665:Binding Sites; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology*; D002642:Chick Embryo; D004627:Embryonic Induction; D053823:Hedgehog Proteins; D051379:Mice; D009046:Motor Neurons / Q000166:cytology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009672:Notochord / Q000196:embryology; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins; D016378:Tissue Transplantation; D015534:Trans-Activators
chemical_list: D000906:Antibodies; D053823:Hedgehog Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators