Inhibition of neuroepithelial patched-induced apoptosis by sonic hedgehog.
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.
Thibert
Chantal
C
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
MA
Lapointe
Françoise
F
Mazelin
Laetitia
L
Le Douarin
Nicole M
NM
Mehlen
Patrick
P
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002642:Chick Embryo; D018274:Electroporation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D053823:Hedgehog Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D015534:Trans-Activators; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases