The proper formation of neuronal circuits within the developing cerebral cortex is dependent upon the migration of two types of neurons, glutamatergic pyramidal neurons (excitatory) and gabaergic interneurons (inhibitory). Deficits in the migration of these neurons have been linked to neuropathologies such as schizophrenia and epilepsy. We recently showed that the transcription factor Neurogenin 2 (Ngn2) specifies the migration properties and dendritic morphology of glutamatergic neurons. Through a recent subtractive hybridization screen we identified formin binding protein 2, (FNBP2) as a candidate gene that might mediate the effects of Ngn2. FNBP2 is expressed in the ventricular zone of the cortex, where glutamatergic neurons initiate migration. Furthermore, sequence analysis identifies domains that are consistent with a role in regulating protein-protein interactions and cytoskeletal dynamics. Since the pattern expression and domain structure of FNBP2 suggest a potential role in regulating neuronal migration within the cortex, the aim of this proposal is to determine the role of FNBP2 in the migration of cortical glutamatergic neurons using a structure-function analysis, and gain and loss of function approaches. ? ? ?
| Guerrier, Sabrice; Coutinho-Budd, Jaeda; Sassa, Takayuki et al. (2009) The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis. Cell 138:990-1004 |
