Sensory experience influences brain development by by activating neural circuits. The activation of these pathways leads to calcium-dependent regulation of various aspects of neuronal function such as synaptic plasticity, cell survival, and axonal and dendritic remodeling. In most of these instances calcium signals exert long-lasting cellular effects by activating transcription factors that induce expression of target genes. Our overall goal is to gain insight into the mechanisms by which calcium signals influence brain development via transcriptional activation. Calcium-regulated transcription factors have historically been identified based on promoter analysis of target genes, and that approach has led to the identification of functionally important transcription factors such as CREB. The promoter analysis approach, while effective, is not suited for comprehensive identification of transcription factors, specially if the target genes are not known. To identify calcium-activated transcription factors and to evaluate their role in cortical development we have developed a new screen that can be used to clone calcium-activated transcription factors in neurons without prior knowledge of the target genes. Using this screen we have discovered that the bHLH protein Neuro-D2 is a calcium-activated transcription factor.
The aims of this proposal are to characterize the molecular mechanisms that regulate Neuro-D2-mediated transcription, and to evaluate the role of Neuro-D2 in cortical development and plasticity based on analysis of mice that have a targeted disruption of the Neuro-D2 gene.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH068830-05
Application #
7553537
Study Section
Special Emphasis Panel (ZMH1)
Project Start
2007-07-01
Project End
2008-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
5
Fiscal Year
2007
Total Cost
$370,916
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Huang, Guo N (2012) T Cell Calcium Mobilization Study (Flow Cytometry). Bio Protoc 2:
Huang, Guo N (2012) Biotinylation of Cell Surface Proteins. Bio Protoc 2:
Zou, Jia; Zhou, Liang; Du, Xiao-Xia et al. (2011) Rheb1 is required for mTORC1 and myelination in postnatal brain development. Dev Cell 20:97-108
Lee, Kyu Pil; Yuan, Joseph P; Zeng, Weizhong et al. (2009) Molecular determinants of fast Ca2+-dependent inactivation and gating of the Orai channels. Proc Natl Acad Sci U S A 106:14687-92
Yuan, Joseph P; Kim, Min Seuk; Zeng, Weizhong et al. (2009) TRPC channels as STIM1-regulated SOCs. Channels (Austin) 3:221-5
Kim, Min Seuk; Zeng, Weizhong; Yuan, Joseph P et al. (2009) Native Store-operated Ca2+ Influx Requires the Channel Function of Orai1 and TRPC1. J Biol Chem 284:9733-41
Yuan, Joseph P; Zeng, Weizhong; Dorwart, Michael R et al. (2009) SOAR and the polybasic STIM1 domains gate and regulate Orai channels. Nat Cell Biol 11:337-43
Park, Sungjin; Park, Joo Min; Kim, Sangmok et al. (2008) Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD. Neuron 59:70-83
Zeng, Weizhong; Yuan, Joseph P; Kim, Min Seuk et al. (2008) STIM1 gates TRPC channels, but not Orai1, by electrostatic interaction. Mol Cell 32:439-48
Shin, Jung Hoon; Kim, Yu Shin; Linden, David J (2008) Dendritic glutamate release produces autocrine activation of mGluR1 in cerebellar Purkinje cells. Proc Natl Acad Sci U S A 105:746-50

Showing the most recent 10 out of 28 publications