Boys and girls show differential susceptibility to diseases such as dyslexia, autism and attention deficit hyperactivity disorder, in part due to differences in brain development. Previous studies suggest that sexual dimorphisms of brain structure and gene expression reflect not only the influence of gonadal hormones, but also direct effects of sex chromosome genes. This project examines differential expression of specific X chromosome genes in male and female mice and their effects on brain development, especially in the cerebral cortex. This objective of this project is to test the hypothesis that differential expression of Xlr3 genes (which encode chromatin binding proteins) regulates neural precursor proliferation, differentiation, migration, downstream gene expression, and morphology. This objective will be accomplished through 3 Specific Aims: (1) analyze the expression of Xlr3 genes in developing male and female brains;(2) identify downstream genes regulated by differential Xlr3 expression;and (3) characterize neurodevelopmental functions of Xlr3 genes through gain- and loss-of-function assays in embryonic cerebral cortex in vivo. This project will thus elucidate gender differences in brain development that may contribute to disease susceptibility. .

Public Health Relevance

Currently, it is unknown why boys and girls have different susceptibility to conditions such as autism, dyslexia, and major depression. One possibility is that sex chromosomes cause subtle differences in male and female brain development. This project investigates how X chromosome genes are differentially expressed and affect neurogenesis in male and female brain development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH099628-02
Application #
8600323
Study Section
Special Emphasis Panel (ZMH1-ERB-L (07))
Program Officer
Panchision, David M
Project Start
2013-01-01
Project End
2014-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
2
Fiscal Year
2014
Total Cost
$211,163
Indirect Cost
$88,881
Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98105
Deng, Xinxian; Berletch, Joel B; Nguyen, Di K et al. (2014) X chromosome regulation: diverse patterns in development, tissues and disease. Nat Rev Genet 15:367-78