Floor-plate-derived netrin-1 is dispensable for commissural axon guidance

Article

关键词: EXPRESSION PATTERN;    CELL;    PROTEIN;    RIG-1/ROBO3;    REGULATOR;    HINDBRAIN;    GRADIENT;    FAMILY;    MICE;   

DOI  :  10.1038/nature22331

来源: SCIE

【 摘 要 】

Netrin-1 is an evolutionarily conserved, secreted extracellular matrix protein involved in axon guidance at the central nervous system midline(1,2). Netrin-1 is expressed by cells localized at the central nervous system midline, such as those of the floor plate in vertebrate embryos(1,3). Growth cone turning assays and three-dimensional gel diffusion assays have shown that netrin-1 can attract commissural axons(2,4-6). Loss-of-function experiments further demonstrated that commissural axon extension to the midline is severely impaired in the absence of netrin-1 (refs 3, 7-9). Together, these data have long supported a model in which commissural axons are attracted by a netrin-1 gradient diffusing from the midline. Here we selectively ablate netrin-1 expression in floor-plate cells using a Ntn1 conditional knockout mouse line. We find that hindbrain and spinal cord commissural axons develop normally in the absence of floor-plate-derived netrin-1. Furthermore, we show that netrin-1 is highly expressed by cells in the ventricular zone, which can release netrin-1 at the pial surface where it binds to commissural axons. Notably, Ntn1 deletion from the ventricular zone phenocopies commissural axon guidance defects previously described in Ntn1-knockout mice. These results show that the classical view that attraction of commissural axons is mediated by a gradient of floor-plate-derived netrin-1 is inaccurate and that netrin-1 primarily acts locally by promoting growth cone adhesion.

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