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General Comment |
The Wnt genes belong to a family of protooncogenes with at least 13 known members
that are expressed in species ranging from Drosophila to man. The name Wnt denotes
the relationship of this family to the Drosophila segment polarity gene 'wingless' and to
its vertebrate ortholog, Int1, a mouse protooncogene.
NCBI Summary:
The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 97%, 85%, and 63% amino acid identity with mouse, chicken, and Xenopus Wnt11 protein, respectively. This gene may play roles in the development of skeleton, kidney and lung, and is considered to be a plausible candidate gene for High Bone Mass Syndrome. [provided by RefSeq, Jul 2008]
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Comment |
Albert Ricken et al reported the
Wnt Signaling in the Ovary and the identification and Compartmentalized Expression of wnt-2, wnt-2b, and Frizzled-4 mRNAs .
Using RT-PCR with degenerate primers on RNA from ovaries of hormone-stimulated immature rats, the authors identified transcripts for wnt-2 and wnt-2b. RT-PCR and in situ hybridization (ISH) demonstrated that granulosa cells express wnt-2 mRNA.. RT-PCR analysis, using primers designed from this wnt-2b cDNA sequence, failed to detect transcripts in the ovarian follicular compartment (granulosa and oocyte). ISH revealed that the ovarian surface epithelium expresses wnt-2b mRNA.
Using a similar degenerate RT-PCR approach, the authors detected expression of a putative wnt receptor, frizzled-4 (fzd-4), and a cytoplasmic component of the wnt signaling cascade, disheveled-2 (dsh-2), in the rat ovary. Further analyses using both RT-PCR and ISH indicated that granulosa cells express fzd-4 mRNA.
RT-PCR, using degenerate and specific primers for wnts, on RNA from five ovarian cancer cell lines confirmed the expression of transcripts for wnt-2b. Two additional wnt transcripts (wnt-5a and wnt-11) were detected in the cancer cell lines and in the rat ovary.
These results demonstrate that transcripts corresponding to components of the wnt signaling cascade are expressed in the immature rat ovary. The localization of these transcripts in specific ovarian compartments suggests that this signal transduction pathway may be involved in follicular development and ovarian function. Furthermore, because wnts have been implicated in the oncogenic transformation of epithelial cells, our results raise the possibility that aberrant wnt expression may be involved in ovarian tumorigenesis in humans.
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Mutations |
1 mutations
Species: mouse
Mutation name:
type: null mutation
fertility: fertile
Comment: WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling. Abedini A et al. (2015) Whereas the roles of the canonical wingless-type MMTV (mouse mammary tumor virus) integration site family (WNT) signaling pathway in the regulation of ovarian follicle growth and steroidogenesis are now established, noncanonical WNT signaling in the ovary has been largely overlooked. Noncanonical WNTs, including WNT5a and WNT11, are expressed in granulosa cells (GCs) and are differentially regulated throughout follicle development, but their physiologic roles remain unknown. Using conditional gene targeting, we found that GC-specific inactivation of Wnt5a (but not Wnt11) results in the female subfertility associated with increased follicular atresia and decreased rates of ovulation. Microarray analyses have revealed that WNT5a acts to down-regulate the expression of FSH-responsive genes in vitro, and corresponding increases in the expression of these genes have been found in the GCs of conditional knockout mice. Unexpectedly, we found that WNT5a regulates its target genes not by signaling via the WNT/Ca(2+) or planar cell polarity pathways, but rather by inhibiting the canonical pathway, causing both β-catenin (CTNNB1) and cAMP responsive element binding (CREB) protein levels to decrease via a glycogen synthase kinase-3β-dependent mechanism. We further found that WNT5a prevents follicle-stimulating hormone and luteinizing protein from up-regulating the CTNNB1 and CREB proteins and their target genes, indicating that WNT5a functions as a physiologic inhibitor of gonadotropin signaling. Together, these findings identify WNT5a as a key regulator of follicle development and gonadotropin responsiveness.-Abedini, A., Zamberlam, G., Lapointe, E., Tourigny, C., Boyer, A., Paquet, M., Hayashi, K., Honda, H., Kikuchi, A., Price, C., Boerboom, D. WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling.//////////////////
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