Reduced fertility with impairment of early-stage embryos observed in mice lacking Lgr4 in epithelial tissues

Mohri, Yasuaki; Umezu, Tomohiro; Hidema, Shizu; Tomisawa, Hayato; Akamatsu, Atsushi; Kato, Shigekí; Nawa, Akihiro; Nishimori, Katsuhiko

doi:10.1016/j.fertnstert.2010.05.050

Cited by 29 publications

(29 citation statements)

References 25 publications

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“…More recently, Lgr4 insufficiency has been shown to cause impaired morphogenesis of other organs such as epididymis and efferent ducts (Mendive et al, 2006;Hoshii et al, 2007;Li et al, 2010), eyelid (Kato et al, 2007), gall bladder (Yamashita et al, 2009), cystic duct (Yamashita et al, 2009), erythroid precursor cells (Song et al, 2008), iris , bone (Luo et al, 2009), and hair follicle (Mohri et al, 2008). We have also shown that Lgr4 has a critical function in the reproductive organs of female mice (Mohri et al, 2010). As yet, however, the ligand(s) for Lgr4 remains unidentified, as do the mechanisms by which Lgr4 regulates kidney morphogenesis.…”

Section: Introductionmentioning

confidence: 58%

Lgr4‐deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3

Mohri

Oyama

Akamatsu

et al. 2011

Developmental Dynamics

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We previously reported that Lgr4 has a critical role in the morphogenesis of kidney, but the detailed functions of Lgr4 in kidney development have not been elucidated. In contrast to Lgr4 null mice with 129Ola 3 C57BL/6J mixed background, C57BL/6J-backcrossed Lgr4 null mice (Lgr4 2/2 ) showed the severe phenotype of embryonic lethality and also had dilated tubules in kidneys at E16.5. Based on quantitative RT-PCR and in situ hybridization, branching morphogenesis at E15.5 in the Lgr4 2/2 was arrested earlier, and both DBAlectin staining and immunohistochemical analysis using Aqp3 antibodies showed that the ureteric bud (UB) of Lgr4 2/2 kidneys underwent premature differentiation. Furthermore, quantitative RT-PCR and histological analysis suggested that the impaired UB differentiation was caused by down-regulation of the Wnt pathway and Gata3 in the Lgr4 2/2 kidneys. We demonstrate here that Lgr4 has a novel function for maintaining the UB in an undifferentiated state. Developmental Dynamics 240:1626-1634,

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Section: Introductionmentioning

confidence: 58%

Lgr4‐deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3

Mohri

Oyama

Akamatsu

et al. 2011

Developmental Dynamics

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“…Most animals that survived until birth died in the first days after Kato et al 2006). Neonatal null mice displayed a variety of abnormalities: male infertility Hoshii et al 2007;Li et al 2010;Mohri et al 2010;Qian et al 2013), impaired prostate development , defective uterine development (Sone et al 2013), delayed development of mammary ducts Wang et al 2013c), severe abnormalities in the anterior segment of the eye (Song et al 2008;Weng et al 2008), abnormal erythropoiesis (Song et al 2008), defective osteoblast differentiation (Luo et al 2009), renal defects (Kato et al 2006;Mohri et al 2011), defective development of the gall bladder (Yamashita et al 2009), eye-open phenotype (Kato et al 2007;Jin et al 2008), and abnormalities in hair follicle development (Mohri et al 2008). In addition, ablation of Lgr4 in mice appears to promote the white-to-brown fat switch, leading to energy expenditure (Wang et al 2013b).…”

Section: Lgr5 Marks Intestinal Stem Cellsmentioning

confidence: 99%

The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength

et al. 2014

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Lgr5 was originally discovered as a common Wnt target gene in adult intestinal crypts and colon cancer. It was subsequently identified as an exquisite marker of multiple Wnt-driven adult stem cell types. Lgr5 and its homologs, Lgr4 and Lgr6, constitute the receptors for R-spondins, potent Wnt signal enhancers and stem cell growth factors. The Lgr5/R-spondin complex acts by neutralizing Rnf43 and Znrf3, two transmembrane E3 ligases that remove Wnt receptors from the stem cell surface. Rnf43/Znrf3 are themselves encoded by Wnt target genes and constitute a negative Wnt feedback loop. Thus, adult stem cells are controlled by an intricate interplay of potent Wnt agonists, antagonists, and anti-antagonists.

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“…Lgr4 is widely expressed in the proliferative (Snippert et al, 2010a) PRIMER Development 140 (12) compartments of many embryonic and adult tissues in vivo (Van Schoore et al, 2005) and it is therefore not surprising that loss-offunction mutations in this family member adversely affect the development or function of multiple organs, including the kidneys, liver, mammary glands, intestine, reproductive tract and skin Kato et al, 2006;Kato et al, 2007;Mohri et al, 2008;Mohri et al, 2011;Mohri et al, 2012;Mohri et al, 2010;Mustata et al, 2011;Oyama et al, 2011). As a result of such pleiotropic effects, Lgr4-null mutations are usually fatal.…”

Section: Lgr Proteins: Functions and Mechanisms Of Action In Adult Stmentioning

confidence: 99%

Lgr proteins in epithelial stem cell biology

Barker

Tan

Clevers³

2013

Development

137

127

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SummaryThe ultimate success of global efforts to exploit adult stem cells for regenerative medicine will depend heavily on the availability of robust, highly selective stem cell surface markers that facilitate the isolation of stem cells from human tissues. Any subsequent expansion or manipulation of isolated stem cells will also require an intimate knowledge of the mechanisms that regulate these cells, to ensure maintenance of their regenerative capacities and to minimize the risk of introducing undesirable growth traits that could pose health risks for patients. A subclass of leucine-rich repeat-containing G-protein-coupled receptor (Lgr) proteins has recently gained prominence as adult stem cell markers with crucial roles in maintaining stem cell functions. Here, we discuss the major impact that their discovery has had on our understanding of adult stem cell biology in various selfrenewing tissues and in accelerating progress towards the development of effective stem cell therapies.

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Reduced fertility with impairment of early-stage embryos observed in mice lacking Lgr4 in epithelial tissues

Cited by 29 publications

References 25 publications

Lgr4‐deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3

Lgr4‐deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3

The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength

Lgr proteins in epithelial stem cell biology

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