Lgr4 Controls Specialization of Female Gonads in Mice

Masae Koizumi; Kazunori Oyama; Yukiko Yamakami; Tomoyo Kida; Ryo Satoh; Shigeki Kato; Shizu Hidema; Tomoyuki Oe; Takaaki Goto; Hans Clevers; Akihiro Nawa; Katsuhiko Nishimori

doi:10.1095/biolreprod.114.123638

Lgr4 Controls Specialization of Female Gonads in Mice

Masae Koizumi, Kazunori Oyama, Yukiko Yamakami, Tomoyo Kida, Ryo Satoh, Shigeki Kato, Shizu Hidema, Tomoyuki Oe, Takaaki Goto, Hans Clevers, Akihiro Nawa, Katsuhiko Nishimori

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

21 Citaten (Scopus)

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Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is a type of membrane receptor with a seven-transmembrane structure. LGR4 is homologous to gonadotropin receptors, such as follicle-stimulating hormone receptor (Fshr) and luteinizing hormone/choriogonadotropin receptor (Lhcgr). Recently, it has been reported that Lgr4 is a membrane receptor for R-spondin ligands, which mediate Wnt/beta-catenin signaling. Defects of R-spondin homolog (Rspo1) and wingless-type MMTV integration site family, member 4 (Wnt4) cause masculinization of female gonads. We observed that Lgr4(-/-) female mice show abnormal development of the Wolffian ducts and somatic cells similar to that in the male gonads. Lgr4(-/-) female mice exhibited masculinization similar to that observed in Rspo1-deficient mice. In Lgr4(-/-) ovarian somatic cells, the expression levels of lymphoid enhancer-binding factor 1 (Lefl) and Axin2 (Axin2), which are target genes of Wnt/beta-catenin signaling, were lower than they were in wild-type mice. This study suggests that Lgr4 is critical for ovarian somatic cell specialization via the cooperative signaling of Rspo1 and Wnt/beta-catenin.

Originele taal-2	Engels
Pagina's (van-tot)	90
Tijdschrift	Biology of Reproduction
Volume	93
Nummer van het tijdschrift	4
DOI's	https://doi.org/10.1095/biolreprod.114.123638
Status	Gepubliceerd - okt. 2015

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10.1095/biolreprod.114.123638

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@article{766e67a2558147db92cb2267c1e1fa96,

title = "Lgr4 Controls Specialization of Female Gonads in Mice",

abstract = "Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is a type of membrane receptor with a seven-transmembrane structure. LGR4 is homologous to gonadotropin receptors, such as follicle-stimulating hormone receptor (Fshr) and luteinizing hormone/choriogonadotropin receptor (Lhcgr). Recently, it has been reported that Lgr4 is a membrane receptor for R-spondin ligands, which mediate Wnt/beta-catenin signaling. Defects of R-spondin homolog (Rspo1) and wingless-type MMTV integration site family, member 4 (Wnt4) cause masculinization of female gonads. We observed that Lgr4(-/-) female mice show abnormal development of the Wolffian ducts and somatic cells similar to that in the male gonads. Lgr4(-/-) female mice exhibited masculinization similar to that observed in Rspo1-deficient mice. In Lgr4(-/-) ovarian somatic cells, the expression levels of lymphoid enhancer-binding factor 1 (Lefl) and Axin2 (Axin2), which are target genes of Wnt/beta-catenin signaling, were lower than they were in wild-type mice. This study suggests that Lgr4 is critical for ovarian somatic cell specialization via the cooperative signaling of Rspo1 and Wnt/beta-catenin.",

author = "Masae Koizumi and Kazunori Oyama and Yukiko Yamakami and Tomoyo Kida and Ryo Satoh and Shigeki Kato and Shizu Hidema and Tomoyuki Oe and Takaaki Goto and Hans Clevers and Akihiro Nawa and Katsuhiko Nishimori",

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year = "2015",

month = oct,

doi = "10.1095/biolreprod.114.123638",

language = "English",

volume = "93",

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T1 - Lgr4 Controls Specialization of Female Gonads in Mice

AU - Koizumi, Masae

AU - Oyama, Kazunori

AU - Yamakami, Yukiko

AU - Kida, Tomoyo

AU - Satoh, Ryo

AU - Kato, Shigeki

AU - Hidema, Shizu

AU - Oe, Tomoyuki

AU - Goto, Takaaki

AU - Clevers, Hans

AU - Nawa, Akihiro

AU - Nishimori, Katsuhiko

PY - 2015/10

Y1 - 2015/10

N2 - Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is a type of membrane receptor with a seven-transmembrane structure. LGR4 is homologous to gonadotropin receptors, such as follicle-stimulating hormone receptor (Fshr) and luteinizing hormone/choriogonadotropin receptor (Lhcgr). Recently, it has been reported that Lgr4 is a membrane receptor for R-spondin ligands, which mediate Wnt/beta-catenin signaling. Defects of R-spondin homolog (Rspo1) and wingless-type MMTV integration site family, member 4 (Wnt4) cause masculinization of female gonads. We observed that Lgr4(-/-) female mice show abnormal development of the Wolffian ducts and somatic cells similar to that in the male gonads. Lgr4(-/-) female mice exhibited masculinization similar to that observed in Rspo1-deficient mice. In Lgr4(-/-) ovarian somatic cells, the expression levels of lymphoid enhancer-binding factor 1 (Lefl) and Axin2 (Axin2), which are target genes of Wnt/beta-catenin signaling, were lower than they were in wild-type mice. This study suggests that Lgr4 is critical for ovarian somatic cell specialization via the cooperative signaling of Rspo1 and Wnt/beta-catenin.

AB - Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is a type of membrane receptor with a seven-transmembrane structure. LGR4 is homologous to gonadotropin receptors, such as follicle-stimulating hormone receptor (Fshr) and luteinizing hormone/choriogonadotropin receptor (Lhcgr). Recently, it has been reported that Lgr4 is a membrane receptor for R-spondin ligands, which mediate Wnt/beta-catenin signaling. Defects of R-spondin homolog (Rspo1) and wingless-type MMTV integration site family, member 4 (Wnt4) cause masculinization of female gonads. We observed that Lgr4(-/-) female mice show abnormal development of the Wolffian ducts and somatic cells similar to that in the male gonads. Lgr4(-/-) female mice exhibited masculinization similar to that observed in Rspo1-deficient mice. In Lgr4(-/-) ovarian somatic cells, the expression levels of lymphoid enhancer-binding factor 1 (Lefl) and Axin2 (Axin2), which are target genes of Wnt/beta-catenin signaling, were lower than they were in wild-type mice. This study suggests that Lgr4 is critical for ovarian somatic cell specialization via the cooperative signaling of Rspo1 and Wnt/beta-catenin.

U2 - 10.1095/biolreprod.114.123638

DO - 10.1095/biolreprod.114.123638

M3 - Article

C2 - 26333992

SN - 0006-3363

VL - 93

SP - 90

JO - Biology of Reproduction

JF - Biology of Reproduction

IS - 4

ER -

Lgr4 Controls Specialization of Female Gonads in Mice

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