The long-term objective of this proposal is to understand how genes specify the structure, functioning and development of a behavioral network. Toward this end, the anatomically simple egg-laying system of the nematode Caenorhabditis elegans will be analyzed. Mutants abnormal in egg laying will be used to define both the neurons that function in egg laying and the genes that specify the development of those neurons. The functional roles of neurons implicated in egg laying by anatomical and/or genetical studies will be tested by surgically removing those neurons using a laser microbeam. In these ways it should be possible to elucidate the complete neural circuit responsible for controlling egg laying, from the chemosensory neurons in the head to the serotoninergic HSN motor neurons that innervate the vulval and uterine muscles and drive egg laying. These studies should reveal how the nervous system responds to information in the environment to control not only egg laying but also feeding behavior, defecation and locomotion, all of which are coordinately regulated with egg laying. Thus, this project should provide novel insights concerning information processing by a nervous system, i.e. how a neural circuit senses and integrates multiple sensory inputs to bring about an appropriate army of behavioral responses. Detailed genetic and molecular genetic studies of genes that affect the HSN motor neurons should reveal molecular mechanisms responsible for specific HSN characteristics, including cell migration, axonal outgrowth, neurotransmitter expression and synapse formation. This information should increase our understanding of how the complexity of the nervous system is specified by the genome. Knowledge of how genes specify the development and functioning of the nervous system as well as of how mutations cause nervous system dysfunction could lead to the understanding and cure of various human neurological disorders. In addition, information gained from these studies concerning nematode behavior and neurobiology could help in the prevention and/or treatment of diseases caused by parasitic nematodes, which are a major source of human suffering in the world today.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM024663-22
Application #
2857077
Study Section
Special Emphasis Panel (NSS)
Project Start
1978-01-01
Project End
2000-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
22
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Burton, Nicholas O; Dwivedi, Vivek K; Burkhart, Kirk B et al. (2018) Neurohormonal signaling via a sulfotransferase antagonizes insulin-like signaling to regulate a Caenorhabditis elegans stress response. Nat Commun 9:5152
Burton, Nicholas O; Furuta, Tokiko; Webster, Amy K et al. (2017) Insulin-like signalling to the maternal germline controls progeny response to osmotic stress. Nat Cell Biol 19:252-257
Luo, Shuo; Horvitz, H Robert (2017) The CDK8 Complex and Proneural Proteins Together Drive Neurogenesis from a Mesodermal Lineage. Curr Biol 27:661-672
Paquin, Nicolas; Murata, Yasunobu; Froehlich, Allan et al. (2016) The Conserved VPS-50 Protein Functions in Dense-Core Vesicle Maturation and Acidification and Controls Animal Behavior. Curr Biol 26:862-71
Bhatla, Nikhil; Droste, Rita; Sando, Steven R et al. (2015) Distinct Neural Circuits Control Rhythm Inhibition and Spitting by the Myogenic Pharynx of C. elegans. Curr Biol 25:2075-89
Ma, Dengke K; Li, Zhijie; Lu, Alice Y et al. (2015) Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids. Cell 161:1152-1163
Bhatla, Nikhil; Horvitz, H Robert (2015) Light and hydrogen peroxide inhibit C. elegans Feeding through gustatory receptor orthologs and pharyngeal neurons. Neuron 85:804-18
de la Cruz, Ignacio Perez; Ma, Long; Horvitz, H Robert (2014) The Caenorhabditis elegans iodotyrosine deiodinase ortholog SUP-18 functions through a conserved channel SC-box to regulate the muscle two-pore domain potassium channel SUP-9. PLoS Genet 10:e1004175
Ma, Dengke K; Rothe, Michael; Zheng, Shu et al. (2013) Cytochrome P450 drives a HIF-regulated behavioral response to reoxygenation by C. elegans. Science 341:554-8
Ma, Long; Gao, Xiaoyang; Luo, Jintao et al. (2012) The Caenorhabditis elegans gene mfap-1 encodes a nuclear protein that affects alternative splicing. PLoS Genet 8:e1002827

Showing the most recent 10 out of 118 publications