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PMID: 12907805 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of neuroepithelial patched-induced apoptosis by sonic hedgehog.

Science (New York, N.Y.) ·Vol. 301 ·No. 5634 ·2003-08-08 ·Pages 843-6

Thibert C, Teillet MA, Lapointe F, Mazelin L, Le Douarin NM, Mehlen P

Abstract

During early development in vertebrates, Sonic hedgehog (Shh) is produced by the notochord and the floor plate. A ventrodorsal gradient of Shh directs ventrodorsal patterning of the neural tube. However, Shh is also required for the survival of neuroepithelial cells. We show that Patched (Ptc) induces apoptotic cell death unless its ligand Shh is present to block the signal. Moreover, the blockade of Ptc-induced cell death partly rescues the chick spinal cord defect provoked by Shh deprivation. Thus, the proapoptotic activity of unbound Ptc and the positive effect of Shh-bound Ptc on cell differentiation probably cooperate to achieve the appropriate spinal cord development.

MeSH Terms

Animals Apoptosis Caspase 3 Caspases/metabolism Cell Differentiation Cell Line Central Nervous System/cytology,embryology,metabolism Chick Embryo Electroporation Epithelial Cells/cytology,metabolism Hedgehog Proteins Humans Intracellular Signaling Peptides and Proteins Membrane Proteins/chemistry,genetics,metabolism Mice Mutation Patched Receptors Patched-1 Receptor Protein Binding Protein Structure, Tertiary Rats Receptors, Cell Surface Signal Transduction Spinal Cord/cytology,embryology Trans-Activators/genetics,metabolism Transfection

Chemicals

Hedgehog Proteins Intracellular Signaling Peptides and Proteins Membrane Proteins Patched Receptors Patched-1 Receptor Ptch1 protein, mouse Receptors, Cell Surface SHH protein, human Trans-Activators CASP3 protein, human Casp3 protein, mouse Casp3 protein, rat Caspase 3 Caspases

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Thibert Chantal

Apoptosis/Differentiation Laboratory, "La Ligue," Molecular and Cellular Genetic Center, CNRS Unite Mixte Recherche (UMR) 5534, University of Lyon, 69622 Villeurbanne, France.

Teillet Marie-Aimée

Lapointe Françoise

Mazelin Laetitia

Le Douarin Nicole M

Mehlen Patrick

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

1095-9203

DOI

10.1126/science.1085405

Published

2003-08-08

Pages

843-6

Language

English

Region

United States

NLM ID

0404511

Subset

Corrections

CommentIn

PMID: 12907783

CommentIn

PMID: 13130129

External Links

PubMed source DOI: 10.1126/science.1085405 View journal details

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Inhibition of neuroepithelial patched-induced apoptosis by sonic hedgehog.

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