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GFR 1-mediated GDNF signalling promotes the differentiation and tangential migration of cortical GABAergic neurons

GDNF signalling via GFR1 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 for those cells in organotypic slice cultures. All the effects of GDNF observed required GFR1 but neither RET nor NCAM, the two transmembrane signalling receptors known for GDNF. Mutant mice lacking GDNF or GFR1, but neither RET nor NCAM, showed reduced numbers of GABAergic cells in the cerebral cortex and hippocampus. Thus, one of the normal functions of GDNF signalling via GFR1 in the developing brain is to support 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.

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Karolinska Institute
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