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Emerging Roles for Hedgehog-Patched-Gli Signal Transduction in Reproduction¹

Children's Memorial Hospital and the Children's Memorial Institute for Education and Research, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60614

Hedgehog (Hh) proteins are expressed during vertebrate development in some tissues with inductive properties and at epithelial-mesenchymal boundaries in several developing organs, including the lung, gut, hair follicle, and tooth. The Hh signaling pathway is highly conserved, and important clues to understanding the mechanism of Hh signal transduction in vertebrates have come from studies in Drosophila. In recent years, Hh signaling has been recognized during embryonic development and in some cases during postnatal life in several mammalian tissues whose functions are essential for reproduction, including the gonads, uterus, and hormonally responsive accessory sex glands such as the prostate and mammary gland. The role of the pathway in these tissues is highly reminiscent of its role at epithelial-mesenchymal-stromal boundaries in other organ systems, which has provided a framework within which to explore Hh signaling in tissues that function in reproduction. Some features unique to these tissues are emerging, including a role in proliferation and differentiation of male germline cells in mammals and apparent influences of sex steroids on Hh signaling. However, many questions remain about the function of Hh signaling in the gonads, uterus, prostate, and mammary gland, including factors regulating the signal transduction pathway, identification of downstream target genes, and roles for Hh signaling in diseases involving these tissues.

¹ This study was supported by National Institutes of Health USPHS grant P01 ES10549.

² Correspondence: David O. Walterhouse, Division of Hematology/Oncology, Box 30, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, 2300 Children's Plaza, Chicago, IL 60614. FAX: 773 880 3223; d-walterhouse{at}northwestern.edu

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