Synaptic connectivity constitutes an integral part of neuronal identity. The recent reconstruction of the connectome of the C.elegans male and its comparison to the long known connectome of the hermaphrodite (a derived female) reveal a sexually dimorphic dimension of neuronal identity: Some defined neuron types that are present in both hermaphrodites and males show sexually dimorphic synaptic connectivity patterns. We propose to dissect the regulatory programs that specify sexual dimorphic identity, as manifested by dimorphic synaptic connectivity features. Specifically, we propose here to (1) reliably and easily visualize sexually dimorphic synaptic connectivity patterns in transgenic animals using GFP-based reporter systems; (2) study aspects of the establishment, maintenance and autonomy of these dimorphic synapses and (3) identify molecules through a candidate gene approach and unbiased profiling approach that genetically program these dimorphic patterns of connectivity and identity. We expect that our studies will provide novel insights into the currentl little explored sexual dimension of neuronal identity.

Public Health Relevance

There are anatomical differences in the brains of males and females in many different species. These anatomical differences are only poorly characterized. Moreover, while some global signals that induce sex differences are well appreciated, the nature of the regulatory programs that instruct dimorphisms in brain anatomy and function are poorly defined. In the roundworm C. elegans anatomical brain differences between its two different sexes have been described in exquisite detail. We propose here to exploit the genetic amenability of C. elegans to analyze how anatomical brain dimorphisms develop and propose to identify genes that are involved in specifying these differences.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37NS039996-17
Application #
9276129
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Morris, Jill A
Project Start
2000-04-01
Project End
2019-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
17
Fiscal Year
2017
Total Cost
$340,708
Indirect Cost
$121,958
Name
Columbia University (N.Y.)
Department
Biochemistry
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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