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

Abstract

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.

Global Gene Expression Profiling of Proliferative Phase Endometrium Reveals Distinct Functional Subdivisions

“…These genes are generally involved in tissues requiring cell renewal including induction of cell proliferation, cell survival, and regulation of differentiation. [13][14][15][16] These changes reflect the rapid growth and development of the functional layer of the human endometrium.…”

The Hedgehog signaling pathway in ovarian teratoma is stimulated by Sonic Hedgehog which induces internalization of Patched

“…It has been shown that the pathway is involved in embryonic development and maturation of Drosophila ovaries, while in the adult fly it is involved in the division of stem cells giving rise to follicles (11). In mammals, the Hh-Gli pathway is also involved in embryonic development of the ovary, and in the adult organism components of the pathway are expressed in reproductive tissues (12). In the adult ovary, the Hh-Gli signaling is active in the granulose cells surrounding the follicle, and it can be additionally activated by exogenous Shh protein (13).…”

Redundant and Differential Roles of Transcription Factors Gli1 and Gli2 in the Development of Mouse Fetal Leydig Cells1

“…The Hh pathway has been implicated in the development and differentiation of the fetal testis [9] and postnatal and adult ovary [10,11]. In the fetal testis, Sertoli cell-derived DHH is responsible for differentiation of the fetal Leydig cells, the primary steroidogenic cell type in the developing testis [12].…”