Programmed cell death in the developing somites is promoted by nerve growth factor via its p75NTR receptor
Programmed cell death in the developing somites is promoted by nerve growth factor via its p75NTR receptor
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DOI：
10.1006/dbio.2000.9948
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发表时间：
2000-12-15
影响因子：
2.7
通讯作者：
Rodríguez-Tébar, A
中科院分区：
文献类型：
--
作者：
Cotrina, ML;González-Hoyuela, M;Rodríguez-Tébar, A
神经营养素通过促进神经元的生成和存活以及调节程序性神经元死亡来控制发育过程中的神经元数量。在后一种情况下，发育中的小鸡视网膜中神经生长因子 (NGF) 诱导的细胞死亡是由常见的神经营养蛋白受体 p75(NTR) 介导的（J. M. Frade、A. Rodriguez-Tebar 和 Y.-A. Barde, 1996, Nature 383, 166-168）。在这里，我们发现 NGF 还诱导发育体节中轴旁中胚层细胞的程序性死亡。 NGF 和 p75(NTR) 均在程序性细胞死亡时和地点的鸡胚体节中表达。此外，用特异性阻断抗体中和内源性 NGF 的活性，或通过应用人 NT-4/5 拮抗 NGF 与 p75(NTR) 的结合，可分别将骨节切开术和皮肌切开术中的凋亡细胞死亡水平降低约 50% 和 70%。之前的数据表明，Sonic Hedgehog对于分化体细胞的生存是必需的。与此一致的是，Sonic hidehog 诱导体节外植体培养物中 NGF mRNA 的减少，从而显示出 NGF 和 Sonic hump 对体细胞存活的拮抗作用。中胚层衍生组织中 NGF/p75(NTR) 对程序性细胞死亡的调节表明神经营养蛋白及其受体具有影响神经系统内外关键发育过程的能力。 (C) 2000 年学术出版社。
Neurotrophins control neuron number during development by promoting the generation and survival of neurons and by regulating programmed neuronal death. In the latter case, the cell death induced by nerve growth factor (NGF) in the developing chick retina is mediated by p75(NTR), the common neurotrophin receptor (J. M. Frade, A. Rodriguez-Tebar, and Y.-A. Barde, 1996, Nature 383, 166-168). Here we show that NGF also induces the programmed death of paraxial mesoderm cells in the developing somites. Both NGF and p75(NTR) are expressed in the somites of chick embryos at the time and the place of programmed cell death. Moreover, neutralizing the activity of endogenous NGF with a specific blocking antibody, or antagonizing NGF binding to p75(NTR) by the application of human NT-4/5, reduces the levels of apoptotic cell death in both the sclerotome and the dermamyotome by about 50 and 70%, respectively. Previous data have shown that Sonic hedgehog is necessary for the survival of differentiated somite cells. Consistent with this, Sonic hedgehog induces a decrease of NGF mRNA in somite explant cultures, thus showing the antagonistic effect of NGF and Sonic hedgehog with respect to somite cell survival. The regulation of programmed cell death by NGF/p75(NTR) in a mesoderm-derived tissue demonstrates the capacity of neurotrophins and their receptors to influence critical developmental processes both within and outside of the nervous system. (C) 2000 Academic Press.