R-spondin, a novel gene with thrombospondin type 1 domain, was expressed in the dorsal neural tube and affected in Wnts mutants

Kamata, Tomoyuki; Katsube, Ken‐ichi; Michikawa, Makoto; Yamada, Masahito; Takada, Shinji; Mizusawa, Hidehiro

doi:10.1016/j.bbaexp.2003.10.009

Cited by 131 publications

(146 citation statements)

References 43 publications

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“…This prediction is consistent with the expression patterns observed for RSpo family members and Wnt ligands in Xenopus and mouse embryos (15,(19)(20)(21)(22)38). Moreover, we have shown that injection of Rspo proteins into adult mice has a strong mitogenic effect on crypt epithelial cells, whereas no obvious proliferative effects are ob- served in other tissues (16,18).…”

Section: Resultssupporting

confidence: 77%

R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6

Binnerts¹,

Kim²,

Bright³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

258

257

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The R-Spondin (RSpo) family of secreted proteins act as potent activators of the Wnt/␤-catenin signaling pathway. We have previously shown that RSpo proteins can induce proliferative effects on the gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular responsiveness to Wnt ligands by modulating the cell-surface levels of the coreceptor LRP6. We show that RSpo1 activity critically depends on the presence of canonical Wnt ligands and LRP6. Although RSpo1 does not directly activate LRP6, it interferes with DKK1/Kremen-mediated internalization of LRP6 through an interaction with Kremen, resulting in increased LRP6 levels on the cell surface. Our results support a model in which RSpo1 relieves the inhibition DKK1 imposes on the Wnt pathway.beta-catenin ͉ DKK1 ͉ Kremen

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Section: Resultssupporting

confidence: 77%

R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6

Binnerts¹,

Kim²,

Bright³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

258

257

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“…A few years ago, Rspo1 (roof platespecific spondin) was the first member of the RSPO family to be identified from screening of genes specifically expressed in the developing spinal cord. It was named for its expression in the roof plate of the neural tube of the mouse embryo and the presence of a protein domain that shares homology with thrombospondin (Kamata et al 2004). That same year, Xenopus R-spondin2 was isolated in a functional screen for its property to activate WNT signaling (Kazanskaya et al 2004).…”

Section: Wnt4 a Wingless Family Gene Involved In Many Biological Promentioning

confidence: 99%

R-spondin1, WNT4, and the CTNNB1 signaling pathway: strict control over ovarian differentiation

Chassot¹,

Gillot²,

Chaboissier³

2014

Reproduction

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Sex differentiation is a unique developmental process. Starting from a bipotential gonad, it gives rise to the ovary and the testis, two highly specialized organs that differ morphologically and physiologically despite sharing common reproductive and endocrine functions. This highlights the specific plasticity of the gonadal precursors and the existence of complex antagonistic genetic regulation. Mammalian sex determination is controlled by paternal transmission of the Y-linked gene, sex-determining region Y (SRY). Using mouse models, it has been shown that the main role of Sry is to activate the expression of the transcription factor Sox9; either one of these two genes is necessary and sufficient to allow testicular development through Sertoli cell differentiation. Thus, defects in SRY/Sry and/or SOX9/Sox9 expression result in male-to-female sex reversal of XY individuals. Molecular mechanisms governing ovarian differentiation remained unknown for a long time, until the discovery of the roles of R-spondin1 (RSPO1) and WNT4. In XX individuals, activation of the b-catenin signaling pathway by the secreted proteins RSPO1 and WNT4 is required to allow granulosa cell differentiation and, in turn, ovarian differentiation. Thus, mutations in RSPO1 result in female-to-male sex reversal of XX patients, and mouse models have allowed the identification of genetic cascades activated by RSPO1 and WNT4 to regulate ovarian development. In this review, we will discuss the respective roles of RSPO1, WNT4, and the b-catenin signaling pathway during ovarian differentiation in mice.Reproduction (2014) 148 R97-R110

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“…The first identified member of this family was human R-spondin 3 . Subsequently, mouse R-spondin1 (roof plate-specific spondin) was discovered as a gene specifically expressed in the roof plate of the neural tube and the dorsal part of telencephalon (Kamata et al 2004), and Xenopus R-spondin2 was isolated in a functional screen for its property to activate Wnt/b-catenin signaling (Kazanskaya et al 2004). Rspos are evolutionarily conserved and are present also in invertebrates, such as hemichordates, chordates, and echinoderms, but not in Drosophila and C. elegans (Kim et al 2006;Yoon and Lee 2012).…”

Section: Wnt Activators R-spondin Protein Familymentioning

confidence: 99%