Cell-autonomous sex determination outside of the gonad

Authors

  • Arthur P. Arnold,

    Corresponding author
    • Department of Integrative Biology and Physiology, and Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, California
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  • Xuqi Chen,

    1. Department of Integrative Biology and Physiology, and Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, California
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  • Jenny C. Link,

    1. Molecular Biology Institute, University of California, Los Angeles, California
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  • Yuichiro Itoh,

    1. Department of Integrative Biology and Physiology, and Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, California
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  • Karen Reue

    1. Molecular Biology Institute, University of California, Los Angeles, California
    2. Departments of Human Genetics and Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California
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Correspondence to: Arthur P. Arnold, Department of Integrative Biology and Physiology, UCLA, 610 Charles Young Drive South, Los Angeles CA 90095-7239. E-mail: arnold@ucla.edu

Abstract

Background: The classic model of sex determination in mammals states that the sex of the individual is determined by the type of gonad that develops, which in turn determines the gonadal hormonal milieu that creates sex differences outside of the gonads. However, XX and XY cells are intrinsically different because of the cell-autonomous sex-biasing action of X and Y genes. Results: Recent studies of mice, in which sex chromosome complement is independent of gonadal sex, reveal that sex chromosome complement has strong effects contributing to sex differences in phenotypes such as metabolism. Adult mice with two X chromosomes (relative to mice with one X chromosome) show dramatically greater increases in body weight and adiposity after gonadectomy, irrespective of their gonadal sex. When fed a high-fat diet, XX mice develop striking hyperinsulinemia and fatty liver, relative to XY mice. The sex chromosome effects are modulated by the presence of gonadal hormones, indicating an interaction of the sex-biasing effects of gonadal hormones and sex chromosome genes. Conclusions: Other cell-autonomous sex chromosome effects are detected in mice in many phenotypes. Birds (relative to eutherian mammals) are expected to show more widespread cell-autonomous sex determination in non-gonadal tissues, because of ineffective sex chromosome dosage compensation mechanisms. Developmental Dynamics 242:371–379, 2013. © 2013 Wiley Periodicals, Inc.

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