Marcos Séverine, Backer Stéphanie, Causeret Frédéric, Tessier-Lavigne Marc, Bloch-Gallego Evelyne
Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France; Inserm, U567, Paris, France.
Mol Cell Neurosci. 2009 Aug;41(4):429-39. doi: 10.1016/j.mcn.2009.04.008. Epub 2009 May 3.
Netrin-1 was previously shown to be required for the tangential migration and survival of neurons that will form the inferior olivary nucleus (ION). Surprisingly, the compared analysis of mutant mice lacking either Netrin-1 or its major receptor DCC reveals striking phenotypic differences besides common features. Although ectopic stops of ION cell bodies occur in the same positions along the migratory stream in both mutants, the ION neurons' number is not affected by the lack of DCC whereas it is reduced in Netrin-1 mutant mice. Thus, cell death results from the absence of Netrin-1 and not from neuron mis-routing, arguing for a role of Netrin-1 as a survival factor in vivo. The secretion of Netrin-1 by the floor plate (FP) is strictly required - whereas DCC is not - to avoid ION axons' repulsion by the FP and allows them to cross it. Leading processes of neurons of other caudal precerebellar nuclei (PCN) cannot cross the FP in either mutant mouse, suggesting differential sensitivity or mechanism of action of Netrin-1 for leading processes of ION and other PCN neurons.
此前研究表明，Netrin-1对于形成下橄榄核（ION）的神经元的切向迁移和存活是必需的。令人惊讶的是，对缺乏Netrin-1或其主要受体DCC的突变小鼠的比较分析揭示了除共同特征外的显著表型差异。尽管在两个突变体中，ION细胞体的异位停滞都发生在迁移流中的相同位置，但ION神经元的数量不受DCC缺乏的影响，而在Netrin-1突变小鼠中则减少。因此，细胞死亡是由于Netrin-1的缺失而非神经元错误布线导致的，这表明Netrin-1在体内作为一种存活因子发挥作用。底板（FP）分泌Netrin-1是避免ION轴突被FP排斥并使其能够穿过FP所严格必需的——而DCC则不是。在任何一种突变小鼠中，其他尾侧小脑前核（PCN）神经元的引导突起都无法穿过FP，这表明Netrin-1对ION和其他PCN神经元的引导突起具有不同的敏感性或作用机制。
