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Sex chromosome genes directly affect brain sexual differentiation

Abstract

Sex differences in the brain are caused by differences in gonadal secretions: higher levels of testosterone during fetal and neonatal life cause the male brain to develop differently than the female brain1. In contrast, genes encoded on the sex chromosomes are not thought to contribute directly to sex differences in brain development, even though male (XY) cells express Y-chromosome genes that are not present in female (XX) cells, and XX cells may have a higher dose of some X-chromosome genes. Using mice in which the genetic sex of the brain (XX versus XY) was independent of gonadal phenotype (testes versus ovaries), we found that XY and XX brain cells differed in phenotype, indicating that a brain cell's complement of sex chromosomes may contribute to its sexual differentiation.

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Figure 1: Sex chromosome effect on neuronal phenotype.

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Acknowledgements

We thank C. Pilgrim, P. Burgoyne, R. Zienecker, G. Noack, J. Xu, J. A. Woodward, A. Garfinkel and C. Lew-Karon for assistance. Supported by the Deutscher Akademischer Austausch Dienst to L.L.C., Deutsche Forschungsgemeinschaft grant RE 413/6-1 to I.R. and NIH grant MH59268 to A.P.A.

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Correspondence to Arthur P. Arnold.

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Carruth, L., Reisert, I. & Arnold, A. Sex chromosome genes directly affect brain sexual differentiation. Nat Neurosci 5, 933–934 (2002). https://doi.org/10.1038/nn922

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