GABAergic neurons are a prominent class of neurons whose dysfunction can results in various disease states. The developmental mechanisms that result in terminal differentiation of GABAergic neurons and the functional properties of many GABAergic neurons are incompletely understood. We propose here to use the experimental advantages of the nematode C.elegans to decipher the gene regulatory events - both on the level of cis-regulatory elements and trans-acting factors - that induce the expression of terminal identity markers of a single GABAergic interneuron (Aim #1) and we propose to study a potential role of this GABAergic interneuron in controlling metabolic states and life span of C. elegans (Aim #2).

Public Health Relevance

We propose to study development and function of a single GABAergic interneuron in the nematode C. elegans using a combination of genetic, molecular and physiological approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS039996-12
Application #
8298644
Study Section
Special Emphasis Panel (ZRG1-MDCN-N (02))
Program Officer
Morris, Jill A
Project Start
2000-04-01
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
12
Fiscal Year
2012
Total Cost
$340,923
Indirect Cost
$126,548
Name
Columbia University (N.Y.)
Department
Biochemistry
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Gendrel, Marie; Atlas, Emily G; Hobert, Oliver (2016) A cellular and regulatory map of the GABAergic nervous system of C. elegans. Elife 5:
Kratsios, Paschalis; Pinan-Lucarré, Bérangère; Kerk, Sze Yen et al. (2015) Transcriptional coordination of synaptogenesis and neurotransmitter signaling. Curr Biol 25:1282-95
Howell, Kelly; White, John G; Hobert, Oliver (2015) Spatiotemporal control of a novel synaptic organizer molecule. Nature 523:83-7
Vidal, Berta; Santella, Anthony; Serrano-Saiz, Esther et al. (2015) C. elegans SoxB genes are dispensable for embryonic neurogenesis but required for terminal differentiation of specific neuron types. Development 142:2464-77
Stefanakis, Nikolaos; Carrera, Ines; Hobert, Oliver (2015) Regulatory Logic of Pan-Neuronal Gene Expression in C. elegans. Neuron 87:733-50
Murgan, Sabrina; Kari, Willi; Rothbächer, Ute et al. (2015) Atypical Transcriptional Activation by TCF via a Zic Transcription Factor in C. elegans Neuronal Precursors. Dev Cell 33:737-45
Gordon, Patricia M; Hobert, Oliver (2015) A competition mechanism for a homeotic neuron identity transformation in C. elegans. Dev Cell 34:206-19
Alqadah, Amel; Hsieh, Yi-Wen; Vidal, Berta et al. (2015) Postmitotic diversification of olfactory neuron types is mediated by differential activities of the HMG-box transcription factor SOX-2. EMBO J 34:2574-89
Zhang, Feifan; Bhattacharya, Abhishek; Nelson, Jessica C et al. (2014) The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in distinct cholinergic and serotonergic neuron types. Development 141:422-35
Cochella, Luisa; Tursun, Baris; Hsieh, Yi-Wen et al. (2014) Two distinct types of neuronal asymmetries are controlled by the Caenorhabditis elegans zinc finger transcription factor die-1. Genes Dev 28:34-43

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