Lgr4 controls specialization of female gonads in mice.
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.
Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan Department of Obstetrics and Gynecology, Ehime University School of Medicine, Toon, Japan.
Masae
M
Koizumi
Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Kazunori
K
Oyama
Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Yukiko
Y
Yamakami
Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Tomoyo
T
Kida
Department of Bio-analytical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Ryo
R
Satoh
Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Shigeki
S
Kato
Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Shizu
S
Hidema
Department of Bio-analytical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Tomoyuki
T
Oe
Department of Bio-analytical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Takaaki
T
Goto
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, University Medical Center Utrecht, Utrecht, The Netherlands.
Hans
H
Clevers
Department of Obstetrics and Gynecology, Ehime University School of Medicine, Toon, Japan.
Akihiro
A
Nawa
Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan knishimori@m.tohoku.ac.jp.
Katsuhiko
K
Nishimori
D000818:Animals; D060466:Axin Protein / Q000096:biosynthesis / Q000235:genetics; D030762:Estrous Cycle / Q000235:genetics / Q000502:physiology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000502:physiology*; D012733:Sex Differentiation / Q000235:genetics; D013480:Superovulation / Q000235:genetics / Q000502:physiology; D019699:Thrombospondins / Q000235:genetics / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000235:genetics; D014928:Wolffian Ducts / Q000254:growth & development
D060466:Axin Protein; C111729:Axin2 protein, mouse; D012739:Gonadal Steroid Hormones; C496200:LGR4 protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; C518903:RSPO1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D019699:Thrombospondins
female reproductive tract; sex differentiation; steroid hormones/steroid hormone receptor; testosterone