Comment |
Expression of repulsive guidance molecule b (RGMb) in the uterus and ovary during the estrous cycle in rats. Meng C 2014 et al.
Repulsive guidance molecule b (RGMb; a.k.a. Dragon), initially identified in the embryonic dorsal root ganglion, is the first member of the RGM family shown to enhance bone morphogenetic protein (BMP) signaling by acting as a BMP co-receptor. BMP signaling has been demonstrated to play an important role in the reproductive organs. Our previous study found that RGMb was expressed in the reproductive axis, but whether RGMb expression in reproductive organs changes across the estrous cycle remains unknown. Here, we show in the rat that RGMb mRNA expression in the uterus was significantly higher during metesterus and diestrus than during proestrus and estrus. Western blotting indicated that RGMb protein was significantly lower during estrus compared with the other three stages. Immunohistochemistry revealed that RGMb protein was mainly localized to the uterine luminal and glandular epithelial cells of the endometrium. RGMb mRNA and protein in the ovary remained unchanged during the estrous cycle. RGMb protein was expressed in the oocytes of all follicles. Weak staining for RGMb protein was also found in corpora lutea. RGMb was not detected in granulosa cells and stromal cells. Taken together, RGMb expression in the uterus and ovary across the estrus cycle demonstrate that RGMb may be involved in the regulation of uterine function, follicular development as well as luteal activity.
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Localization and action of Dragon (RGMb), a novel BMP co-receptor, throughout the reproductive axis Xia Y, et al .
Bone morphogenetic proteins (BMPs) play important roles in reproduction including primordial germ cell (PGC) formation, follicular development, spermatogenesis and FSH secretion. Dragon, a recently identified glycosylphosphatidylinositol (GPI)-anchored member of the repulsive guidance molecule (RGM) family, is also a BMP co-receptor. In the present study, we determined the tissue and cellular localization of Dragon in reproductive organs using immunohistochemistry and in situ hybridization. Among reproductive organs, Dragon was expressed in testis, epididymis, ovary, uterus, and pituitary. In the testis of early postnatal mice, Dragon was found in gonocytes and spermatogonia while in immature testes, Dragon was only weakly expressed in spermatogonia. Interestingly, PMSG treatment of immature mice robustly induced Dragon production in spermatocytes. In adult testis, Dragon was found in spermatocytes and round spermatids. In the ovary, Dragon was detected exclusively within oocytes and primarily those within secondary follicles. In the pituitary, Dragon expressing cells overlapped FSH expressing cells. Dragon was also expressed in a number of cell lines originating from reproductive tissues including Ishikawa, Hela, Lbeta T2, MCF-7 and JEG3 cells. Immunocytochemistry and gradient sucrose ultracentrifugation studies showed Dragon was localized in lipid rafts within the plasma membrane. In reproductive cell lines, Dragon expression enhanced signaling of exogenous BMP2 or BMP4. The present studies demonstrate that Dragon expression is dynamically regulated throughout the reproductive tract and that Dragon protein modulates BMP signaling in cells from reproductive tissues. The overlap between Dragon expression and the functional BMP signaling system suggests that Dragon may play a role in mammalian reproduction.
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Mutations |
1 mutations
Species: mouse
Mutation name:
type: null mutation
fertility: fertile
Comment: Repulsive Guidance Molecule b (RGMb) Is Dispensable for Normal Gonadal Function in Mice. Meng C et al. (2016) Bone morphogenetic protein (BMP) signaling plays an important role in spermatogenesis and follicle development. Our previous studies have shown that repulsive guidance molecule b (RGMb, also known as Dragon) is a co-receptor that enhances BMP2 and BMP4 signaling in several cell types, and that RGMb is expressed in spermatocytes and spermatids in the testis, and in oocytes of the secondary follicles in the ovary. Here, we demonstrated that specific deletion of Rgmb in germ cells in the testis and ovary did not alter Smad1/5/8 phosphorylation, gonadal structures and fertility. In addition, ovaries from postnatal global Rgmb knockout mice showed similar structures to the wild type ovaries. Our results suggest that RGMb is not essential for normal gonadal function.//////////////////
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