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 interneurons in the cerebral cortex, and projection neurons in the basal ganglia. 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. This application is a competitive renewal for two NIMH grants: MH49428 and MH51561; the proposed projects herein are a synthesis of the scientific goals of MH49428 and MH51561.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH049428-11
Application #
6576089
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Brady, Linda S
Project Start
1992-06-01
Project End
2007-11-30
Budget Start
2002-12-06
Budget End
2003-11-30
Support Year
11
Fiscal Year
2003
Total Cost
$377,292
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

Pla, Ramon; Stanco, Amelia; Howard, MacKenzie A et al. (2018) Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis. Cereb Cortex 28:3797-3815
An, Joon-Yong; Lin, Kevin; Zhu, Lingxue et al. (2018) Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder. Science 362:
Xu, Zhejun; Liang, Qifei; Song, Xiaolei et al. (2018) SP8 and SP9 coordinately promote D2-type medium spiny neuron production by activating Six3 expression. Development 145:
Dickel, Diane E; Ypsilanti, Athena R; Pla, Ramón et al. (2018) Ultraconserved Enhancers Are Required for Normal Development. Cell 172:491-499.e15
Li, Jiwen; Wang, Chunyang; Zhang, Zhuangzhi et al. (2018) Transcription Factors Sp8 and Sp9 Coordinately Regulate Olfactory Bulb Interneuron Development. Cereb Cortex 28:3278-3294
Hu, Jia Sheng; Vogt, Daniel; Lindtner, Susan et al. (2017) Coup-TF1 and Coup-TF2 control subtype and laminar identity of MGE-derived neocortical interneurons. Development 144:2837-2851
Hu, Jia Sheng; Vogt, Daniel; Sandberg, Magnus et al. (2017) Cortical interneuron development: a tale of time and space. Development 144:3867-3878
Yang, Nan; Chanda, Soham; Marro, Samuele et al. (2017) Generation of pure GABAergic neurons by transcription factor programming. Nat Methods 14:621-628
Sun, Yishan; Pa?ca, Sergiu P; Portmann, Thomas et al. (2016) A deleterious Nav1.1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients. Elife 5:
Ypsilanti, Athéna R; Rubenstein, John L R (2016) Transcriptional and epigenetic mechanisms of early cortical development: An examination of how Pax6 coordinates cortical development. J Comp Neurol 524:609-29

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