Sex differences in the nervous system and in behavior are ubiquitous in the animal kingdom. Beyond their basic biological interest, these differences have important implications for understanding the sex bias that characterizes many mental health and neurological disorders. An intriguing but poorly understood component of nervous system sex differences arises through the actions of hormone-independent, cell-intrinsic "neural sex" in shaping characteristics of the nervous system. In preliminary work using the nematode C. elegans, we have identified robust sex differences in olfactory behavior that arise through cell-intrinsic, sex-dependent modification of the function of neurons common to both sexes. Understanding the mechanisms that underlie these sex differences has great potential to shed light on similar phenomena acting in the mammalian CNS. In three Specific Aims, we will (1) identify the precise neural foci that regulate sex differences in olfaction, and characterize sex differences in the development and function of these neurons;(2) use a candidate-gene approach as well as targeted microarray studies to identify sex-regulated genes in the core nervous system and determine their functional significance;and (3) characterize the role of C. elegans members of the conserved DM family of sexual regulators, including dmd-3, in generating sex differences in olfaction. Together, this work takes an innovative approach to illuminating the conserved molecular, genetic and neural mechanisms by which neural sex is coupled to sex differences in the development and function of the nervous system. Lay summary Using a tiny soil roundworm, we will examine the genetic and cellular regulation of sex differences in the development and function of the nervous system. These studies will identify genes and mechanisms that may have important roles in human mental health and neurological conditions, such as autism, mood disorders and chronic pain syndrome, that preferentially affect one sex over the other.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM086456-04
Application #
8206543
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Sesma, Michael A
Project Start
2009-01-01
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2013-12-31
Support Year
4
Fiscal Year
2012
Total Cost
$247,533
Indirect Cost
$86,797
Name
University of Rochester
Department
Genetics
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Ryan, Deborah A; Miller, Renee M; Lee, KyungHwa et al. (2014) Sex, age, and hunger regulate behavioral prioritization through dynamic modulation of chemoreceptor expression. Curr Biol 24:2509-17
Mowrey, William R; Bennett, Jessica R; Portman, Douglas S (2014) Distributed effects of biological sex define sex-typical motor behavior in Caenorhabditis elegans. J Neurosci 34:1579-91
Miller, Renee M; Portman, Douglas S (2011) The Wnt/beta-catenin asymmetry pathway patterns the atonal ortholog lin-32 to diversify cell fate in a Caenorhabditis elegans sensory lineage. J Neurosci 31:13281-91