Substantial evidence suggests that neuropsychiatric disorders such as schizophrenia, bipolar disorder, and autism, may result from defects in GABAergic neurotransmission within the forebrain. Identification of factors that control the development and function of GABAergic neurons within the forebrain may provide insights into the underlying causes of these disorders. A set of likely candidate factors include the Dlx family of homeobox transcription factors since they are essential for the proper differentiation and function of forebrain GABAergic neurons. Dlx 1 continues to be expressed in restricted regions of the postnatal mouse brain and may be involved in the maintenance, production, or function of GABAergic neurons in the adult animal. To study the early and postnatal expression of Dlx1+ cells and their projections, a mutant allele of Dlx1 that expresses a cell body marker and an axonal marker from the Dlxl locus will be generated. Using co-labeling methods such as in situ hybridization and immunohistochemistry, the cell types and axonal projections of Dlx1+ cells in the forebrain will be determined. A study of late postnatal defects in Dlxl mutants is prevented since Dlx1 mutants die within a month of birth. To circumvent this problem, the Cre/loxP system will be used to generate a conditional allele of the Dlx 1 mutation. The postnatal role of Dlx 1 in GABAergic neuronal maturation and function will be examined by phenotypic analysis of mice with a temporal and tissue-specific deletion of Dlx1 in forebrain.
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| Long, Jason E; Cobos, Inma; Potter, Greg B et al. (2009) Dlx1&2 and Mash1 transcription factors control MGE and CGE patterning and differentiation through parallel and overlapping pathways. Cereb Cortex 19 Suppl 1:i96-106 |
| Petryniak, Magdalena A; Potter, Gregory B; Rowitch, David H et al. (2007) Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain. Neuron 55:417-33 |
