Thibert Chantal, Teillet Marie-Aimée, Lapointe Françoise, Mazelin Laetitia, Le Douarin Nicole M, Mehlen Patrick
Apoptosis/Differentiation Laboratory, "La Ligue," Molecular and Cellular Genetic Center, CNRS Unite Mixte Recherche (UMR) 5534, University of Lyon, 69622 Villeurbanne, France.
Science. 2003 Aug 8;301(5634):843-6. 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.
在脊椎动物的早期发育过程中，音猬因子（Shh）由脊索和底板产生。Shh的腹背梯度引导神经管的腹背模式形成。然而，神经上皮细胞的存活也需要Shh。我们发现，除非其配体Shh存在以阻断信号，否则patched（Ptc）会诱导凋亡性细胞死亡。此外，阻断Ptc诱导的细胞死亡可部分挽救因Shh缺失引起的鸡脊髓缺陷。因此，未结合的Ptc的促凋亡活性以及与Shh结合的Ptc对细胞分化的积极作用可能共同协作以实现适当的脊髓发育。
