GDNF and GFRalpha1 Promote Differentiation and Tangential Migration of Cortical GABAergic Neurons

Neuron. 2005 Mar 3;45(5):701-13. doi: 10.1016/j.neuron.2005.01.043.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Movement / physiology*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Growth Factors / biosynthesis*
  • Nerve Growth Factors / deficiency
  • Nerve Growth Factors / genetics
  • Neurons / cytology
  • Neurons / metabolism*
  • Organ Culture Techniques
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / biosynthesis*
  • Receptor Protein-Tyrosine Kinases / deficiency
  • Receptor Protein-Tyrosine Kinases / genetics
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Gdnf protein, mouse
  • Gfra1 protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Nerve Growth Factors
  • Proto-Oncogene Proteins
  • gamma-Aminobutyric Acid
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, mouse