Abstract

The central tenet of this proposal is that the Dlx family of homeobox genes is essential for regulating the differentiation and function of forebrain GABAergic neurons. Accordingly, I suggest that the Dlx genes are required for controlling the development, and perhaps the function, of intemeurons in the cerebral cortex, and projection neurons in the basal ganglia. Therefore, understanding the functions of the Dlx genes should yield insights into the roles of GABAergic neurons in forebrain neural systems, and may provide insights into disorders of the forebrain due to defects in GABAergic neurons. The experiments described herein use standard and conditional genetic methods to alter the expression of the Dlx genes in developing mice. These methods will allow us to study the effects of deleting individual and/or multiple Dlx genes on the development and function of forebrain GABAergic neurons. In addition, we will investigate the effects of ectopically expressing the Dlx genes. These studies have implications for understanding the genetic pathways that regulate the specification, differentiation and function of forebrain GABAergic neurons, and have implications for understanding the molecular bases of human disorders of GABAergic neurotransmission.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Award (K05)
Project #
1K05MH065670-01
Application #
6471447
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Brady, Linda S
Project Start
2003-01-01
Project End
2007-12-31
Budget Start
2003-01-01
Budget End
2003-12-31
Support Year
1
Fiscal Year
2003
Total Cost
$120,528
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Wang, Bei; Lufkin, Thomas; Rubenstein, John L R (2011) Dlx6 regulates molecular properties of the striatum and central nucleus of the amygdala. J Comp Neurol 519:2320-34
Wang, Yanling; Dye, Catherine A; Sohal, Vikaas et al. (2010) Dlx5 and Dlx6 regulate the development of parvalbumin-expressing cortical interneurons. J Neurosci 30:5334-45
Maira, Mario; Long, Jason E; Lee, Amie Y et al. (2010) Role for TGF-beta superfamily signaling in telencephalic GABAergic neuron development. J Neurodev Disord 2:48-60
Potter, Gregory B; Petryniak, Magdalena A; Shevchenko, Eugenia et al. (2009) Generation of Cre-transgenic mice using Dlx1/Dlx2 enhancers and their characterization in GABAergic interneurons. Mol Cell Neurosci 40:167-86
Long, Jason E; Swan, Christo; Liang, Winnie S et al. (2009) Dlx1&2 and Mash1 transcription factors control striatal patterning and differentiation through parallel and overlapping pathways. J Comp Neurol 512:556-72
Winden, Kellen D; Oldham, Michael C; Mirnics, Karoly et al. (2009) The organization of the transcriptional network in specific neuronal classes. Mol Syst Biol 5:291
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
Scearce-Levie, K; Roberson, E D; Gerstein, H et al. (2008) Abnormal social behaviors in mice lacking Fgf17. Genes Brain Behav 7:344-54
Faedo, Andrea; Tomassy, Giulio Srubek; Ruan, Youlin et al. (2008) COUP-TFI coordinates cortical patterning, neurogenesis, and laminar fate and modulates MAPK/ERK, AKT, and beta-catenin signaling. Cereb Cortex 18:2117-31
Zhao, Yangu; Flandin, Pierre; Long, Jason E et al. (2008) Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants. J Comp Neurol 510:79-99

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