Sfrp1, Sfrp2, and Sfrp5 regulate the Wnt/β-catenin and the planar cell polarity pathways during early trunk formation in mouse

Vertebrate Body Plan, Center for Developmental Biology, RIKEN Kobe, Minatojima-Minami, Chuou-ku, Kobe, Japan.
genesis (Impact Factor: 2.02). 02/2008; 46(2):spcone. DOI: 10.1002/dvg.20489
Source: PubMed


The secreted frizzled-related protein gene family encodes proteins that regulate Wnt signaling. Msx1 in situ hybridization of 9.5 days post coitus mouse embryos showing normal neural tube development in an Sfrp1; Sfrp2 double mutant (left) but severe neural tube defects in a Looptail (Lp/+); Sfrp1; Sfrp2 triple mutant (right). These findings suggest that Sfrps regulate the Wnt planar cell polarity pathway. See Satoh et al. in this issue.

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Available from: Akihiko Shimono, Sep 25, 2015
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    • "Sfrp1 together with Sfrp2 and Sfrp5, belong to the type 1 subfamily of Sfrp antagonists of the Wnt signaling [96]. Since there is functional redundancy between the members of each subfamily [97], loss of Sfrp1, 2 and 5 in a compound mutant mouse model (Sfrp1 -/-Sfrp2 -/-Sfrp5 +/-) led to dysregulation of the Wnt5a signaling pathway detected by elevated levels of phosphorylated "
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    ABSTRACT: Congenital short bowel syndrome (CSBS) is a rare gastrointestinal disorder in which the mean length of the small intestine is substantially reduced when compared to its normal counterpart. Families with several affected members have been described and CSBS has been suggested to have a genetic basis. Recently, our group found mutations in CLMP as the cause of the recessive form of CSBS, and mutations in FLNA as the cause of the X-linked form of the disease. These findings have improved the quality of genetic counseling for CSBS patients and made prenatal diagnostics possible. Moreover, they provided a reliable starting point to further investigate the pathogenesis of CSBS, and to better understand the development of the small intestine. In this review, we present our current knowledge on CSBS and discuss hypotheses on how the recent genetic findings can help understand the cause of CSBS. Copyright © 2015. Published by Elsevier B.V.
    Biochimica et Biophysica Acta 08/2015; 1852(11). DOI:10.1016/j.bbadis.2015.08.007 · 4.66 Impact Factor
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    • "SFRPs prevent downstream WNT signalling by binding to and sequestering WNT ligands in the extracellular space (Bovolenta et al. 2008). Among SFRPs, SFRP5 may interact with both canonical and non-canonical WNT signalling pathways (Li et al. 2008, Satoh et al. 2008) and might be an import metabolic regulator (Ouchi et al. 2010, Mori et al. 2012, Carstensen et al. 2014). Results from an in vitro study indicated that SFRP5 impairs insulin signalling under normal conditions, but reduces tumour necrosis factor a-induced inflammation in primary human adipocytes (Carstensen et al. 2014). "
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    ABSTRACT: WNT/beta-catenin signalling is involved in regulating adipogenesis, and its dysregulation occurs in obesity. Secreted frizzled-related protein (SFRP) 5 is a WNT protein inhibitor; however, its role in adipogenesis and obesity is controversial. In the present study, we observed that SFRP5 mRNA levels were increased in the fat tissues of obese humans and mice. Sfrp5 expression was gradually induced during white and brown adipocyte differentiation, and was highly enriched in mature adipocytes rather than preadipocytes. However, the exogenous overexpression of Sfrp5 indicated that Sfrp5 may not directly regulate adipogenesis in vitro under the current conditions. Moreover, SFRP5 did not inhibit the canonical WNT/beta-catenin signalling pathway in preadipocytes. Subsequently, we measured circulating SFRP5 levels of obese patients and nonobese subjects using ELISA, and noted no significant difference. Collectively, these findings indicate that Sfrp5 represents a candidate for mature adipocyte marker genes. Our data provide new evidence concerning the role of SFRP5 in white and brown adipogenesis and obesity.
    Journal of Molecular Endocrinology 10/2014; 53(3). DOI:10.1530/JME-14-0037 · 3.08 Impact Factor
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    • "One evolutionarily conserved family of secreted proteins that modulates Wnt signaling in the extracellular matrix is the family of secreted frizzled-related proteins (SFRPs). Sfrp proteins are important for development, such as dorsoventral patterning in zebrafish and Xenopus laevis [9]–[12], brain and retina development in zebrafish and medaka [13], [14], gastrulation in amphioxus [15], and formation of mouse epithelial structures and trunk [16]–[18]. They are also frequently dysregulated in cancers [19], [20]. "
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    ABSTRACT: Sfrp5 belongs to the family of secreted frizzled related proteins (Sfrp), secreted inhibitors of Wingless-MMTV Integration Site (Wnt) signaling, which play an important role in cancer and development. We selected sfrp5 because of its compelling expression profile in the developing endoderm in zebrafish, Danio rerio. In this study, overexpression of sfrp5 in embryos results in defects in both convergent extension (CE) by inhibition of non-canonical Wnt signaling and defects in dorsoventral patterning by inhibition of Tolloid-mediated proteolysis of the BMP inhibitor Chordin. From 25 hours post fertilization (hpf) to 3 days post fertilization (dpf), both overexpression and knockdown of Sfrp5 decrease the size of the endoderm, significantly reducing liver cell number. At 3 dpf, insulin-positive endodermal cells fail to coalesce into a single pancreatic islet. We show that Sfrp5 inhibits both canonical and non-canonical Wnt signaling during embryonic and endodermal development, resulting in endodermal abnormalities.
    PLoS ONE 09/2013; 8(4):e62470. DOI:10.1371/journal.pone.0062470 · 3.23 Impact Factor
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