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. 2025 Mar-Apr:142:100833.
doi: 10.1016/j.diff.2024.100833. Epub 2024 Dec 20.

WNT16 primer

McLean H Williamson  1 , Wilson K Clements  2
Affiliations

WNT16 primer

McLean H Williamson et al. Differentiation. 2025 Mar-Apr.
No abstract available

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Figures

Figure 1.
Figure 1.. WNT16 genomic structure, protein composition, and signaling transduction.
(A) WNT signaling pathways potentiated by WNT16. WNT16 can induce canonical (β-catenin-dependent) or non-canonical (Ca2+ or planar cell polarity) WNT signaling pathways. (B) Genomic features of human isoforms of WNT16: WNT16A and WNT16B. Features unique to WNT16A are shaded in red, features unique to WNT16B are shaded in yellow, and those common between the isoforms are shaded in purple. (C) Protein diagram of human WNT16B protein. Black lollipops mark cysteine residues that participate in disulfide linkages, red lollipops mark N-linked glycosylation sites, and yellow lollipop an O-palmitoleoyl serine residue. GSK3β, glycogen synthase kinase 3 beta; TCF, T cell factor; LEF, lymphoid enhancer factor; LRP6, low-density-lipoprotein-related protein 6; Gαq, Gq protein alpha subunit; PLC, phospholipase C; IP3, inositol triphosphate; CAN, calcineurin; NF-AT, nuclear factor of activated T cells; AP-1, activator protein 1; ROR2, receptor tyrosine kinase-like orphan receptor 2; JNK, c-Jun N-terminal kinase; RAC1: Rac family small GTPase 1.
Figure 2
Figure 2. Wnt16 expression in mouse and zebrafish.
(A) Immunofluorescence shows WNT16 protein in aortic smooth muscle (left) and osteoblasts (right) of adult mice. (B) Whole-mount in situ hybridization in embryonic zebrafish shows wnt16 transcript in the somites (20 somite stage). smAct, smooth muscle actin; BM, bone marrow; C, calvarium. Adapted from REF# ; ; .
Figure 3
Figure 3. Mutant models of Wnt16.
(A) Complete absence of the Wnt16 locus in mice leads to spontaneous tibia fractures and reduced cortical bone mass. (B) Introduction of indels into exon 3 of wnt16 leads to severe skeletal defects and ablates the caudal fin. (C) Mice with an exon 3 Wnt16 knockout on an LDLR−/− background display aberrant aortic morphology. (D) Splice-blocking morpholino (MO) targeting wnt16 decreases runx1-positive and cmyb-positive HSC precursors (red arrowheads) along with rag1-positive T lymphocytes (blue arrowheads) in zebrafish embryos. Adapted from REF# ; ; ; .
Figure 4
Figure 4. Diseases associated with Wnt16 dysregulation.
Diseases associated with Wnt16 dysregulation. (A) Missense polymorphisms altering the expression or function of Wnt16 can lead to the development of systemic lupus erythematosus, basal cell carcinoma, osteoarthritis, and heightened risk for bone fractures. (B) Dysregulated expression of Wnt16 caused by the E2A-PBX1 oncogenic fusion protein can lead to the development of pre-B cell ALL. Heightened Wnt16 expression is seen in breast cancer, ovarian cancer, and prostate cancer, and is correlated with treatment-resistant disease.
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References

    1. Prud’homme B, Lartillot N, Balavoine G, Adoutte A & Vervoort M Phylogenetic analysis of the Wnt gene family. Insights from lophotrochozoan members. Curr. Biol 12, 1395 (2002). - PubMed
    1. McWhirter JR et al. Oncogenic homeodomain transcription factor E2A-Pbx1 activates a novel WNT gene in pre-B acute lymphoblastoid leukemia. Proc. Natl. Acad. Sci. U. S. A 96, 11464–11469(1999). - PMC - PubMed
    1. Moverare-Skrtic S et al. Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures. Nature Med. 20, 1279–1288 (2014). - PMC - PubMed
    1. Tong W et al. Wnt16 attenuates osteoarthritis progression through a PCP/JNK-mTORC1-PTHrP cascade. Ann. Rheum. Dis 78, 551–561 (2019). - PubMed
    1. Wan X et al. WNT16b promotes the proliferation and self-renewal of human limbal epithelial stem/progenitor cells via activating the calcium/calcineurin A/NFATC2 pathway. Cell Prolif. 56, e13460 (2023). - PMC - PubMed

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