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Science 338 (6112): 1357-1360

Copyright © 2012 by the American Association for the Advancement of Science

Sexually Dimorphic BDNF Signaling Directs Sensory Innervation of the Mammary Gland

Yin Liu,1 Michael Rutlin,1,* Siyi Huang,1 Colleen A. Barrick,2 Fan Wang,3 Kevin R. Jones,4 Lino Tessarollo,2 David D. Ginty1,{dagger}

Abstract: How neural circuits associated with sexually dimorphic organs are differentially assembled during development is unclear. Here, we report a sexually dimorphic pattern of mouse mammary gland sensory innervation and the mechanism of its formation. Brain-derived neurotrophic factor (BDNF), emanating from mammary mesenchyme and signaling through its receptor TrkB on sensory axons, is required for establishing mammary gland sensory innervation of both sexes at early developmental stages. Subsequently, in males, androgens promote mammary mesenchymal expression of a truncated form of TrkB, which prevents BDNF-TrkB signaling in sensory axons and leads to a rapid loss of mammary gland innervation independent of neuronal apoptosis. Thus, sex hormone regulation of a neurotrophic factor signal directs sexually dimorphic axonal growth and maintenance, resulting in generation of a sex-specific neural circuit.

1 The Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2 Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute–Frederick, National Institutes of Health, Frederick, MD 21702, USA.
3 Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
4 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.

* Present address: Department of Biology, National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.

{dagger} To whom correspondence should be addressed. E-mail: dginty{at}jhmi.edu



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