GDNF and GFRα1 Promote Differentiation and Tangential Migration of Cortical GABAergic Neurons

Cortical GABAergic neurons are generated in the ventral telencephalon and migrate dorsally into the cortex following a tangential path. GDNF signaling via GFR 1 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 GFR 1 but neither RET nor NCAM, the two transmembrane signaling receptors known for GDNF. Mutant mice lacking GDNF or GFR 1, 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 GFR 1 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.