Inhibition of Neuroepithelial Patched-Induced Apoptosis by Sonic Hedgehog

• Published in: Science (American Association for the Advancement of Science) 2003-08, Vol.301 (5634), p.843-846
• Main Authors: Thibert, Chantal, Teillet, Marie-Aimée, Lapointe, Françoise, Mazelin, Laetitia, Le Douarin, Nicole M., Mehlen, Patrick
• Format: Article
• Language: English
• Subjects: Ageing, cell death; Amygdala; Animals; Apoptosis; Biological and medical sciences; Cancer; Caspase 3; Caspases - metabolism; Cell Behavior; Cell death; Cell Differentiation; Cell growth; Cell Line; Cell membranes; Cell physiology; Cellular Biology; Central Nervous System - cytology; Central Nervous System - embryology; Central Nervous System - metabolism; Chick Embryo; Development Biology; Developmental biology; Electroporation; Embryology and Organogenesis; Embryos; Epithelial Cells - cytology; Epithelial Cells - metabolism; Fear; Fundamental and applied biological sciences. Psychology; Genetic aspects; Hedgehog Proteins; Humans; Individualized Instruction; Intracellular Signaling Peptides and Proteins; Life Sciences; Ligands; Logical Thinking; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Molecular and cellular biology; Morphogenesis; Mutation; Nervous system; Neurons; Patched Receptors; Patched-1 Receptor; Physiological aspects; Protein Binding; Protein Structure, Tertiary; Rats; Receptors; Receptors, Cell Surface; Signal Transduction; Spinal cord; Spinal Cord - cytology; Spinal Cord - embryology; Subcellular Processes; Trans-Activators - genetics; Trans-Activators - metabolism; Transfection; Vertebrates
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1085405

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.