Pozas Esther, Ibáñez Carlos F
Division of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, S-17177 Stockholm, Sweden.
Neuron. 2005 Mar 3;45(5):701-13. doi: 10.1016/j.neuron.2005.01.043.
Cortical GABAergic neurons are generated in the ventral telencephalon and migrate dorsally into the cortex following a tangential path. GDNF signaling via GFRalpha1 was found to promote the differentiation of ventral precursors into GABAergic cells, enhancing their neuronal morphology and motility. GDNF stimulated axonal growth in cortical GABAergic neurons and acted as a potent chemoattractant of GABAergic cells. These effects required GFRalpha1 but neither RET nor NCAM, the two transmembrane signaling receptors known for GDNF. Mutant mice lacking GDNF or GFRalpha1, but neither RET nor NCAM, showed reduced numbers of GABAergic cells in the cerebral cortex and hippocampus. We conclude that one of the normal functions of GDNF signaling via GFRalpha1 in the developing brain is to promote the differentiation and migration of cortical GABAergic neurons. The lack of involvement of RET or NCAM in these processes suggests the existence of additional transmembrane effectors for GDNF.
皮质GABA能神经元在腹侧端脑生成，并沿切线路径背向迁移至皮质。研究发现，通过GFRα1的GDNF信号传导可促进腹侧前体细胞分化为GABA能细胞，增强其神经元形态和运动能力。GDNF刺激皮质GABA能神经元的轴突生长，并作为GABA能细胞的有效化学引诱剂。这些作用需要GFRα1，但不需要RET和NCAM，这是已知的GDNF的两种跨膜信号受体。缺乏GDNF或GFRα1但不缺乏RET和NCAM的突变小鼠，其大脑皮质和海马体中的GABA能细胞数量减少。我们得出结论，在发育中的大脑中，通过GFRα1的GDNF信号传导的正常功能之一是促进皮质GABA能神经元的分化和迁移。RET或NCAM未参与这些过程表明存在GDNF的其他跨膜效应器。
