WNT3A
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Protein Wnt-3a is a protein that in humans is encoded by the WNT3A gene.[5]
The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have are critical in tissue homeostasis, embryonic development, and disease.
Signaling and Related Genes
[edit]WNT3A is highly related to the WNT3 gene in sequence and protein function. WNT3A and WNT3 signal similarly through primarily the beta-catenin/Tcf pathway. WNT3A is located in the genome beside the WNT9A gene across many vertebrates. Similarly, the WNT3 gene occurs in the genome beside the WNT9B gene. WNT9A and WNT9B signal through the beta-catenin/Tcf pathway but do not play related roles as WNT3A and WNT3 in the same cellular processes.
Role in Disease
[edit]WNT3A is not linked to particular genetic disorder in humans. Mice that have a genetic mutation in the WNT3A die during early embryogenesis and fail to correctly form axial tissues.[6] Rodent Wnt3a promotes the beta-catenin/Tcf pathway which is tumor inducing and can cause cancer when expressed in particular cell populations.[7]
Role in embryonic development
[edit]Embryonic development is the process where the body plan is created. From studies in vertebrate model systems we can infer the roles of particular genes in human anatomical structures. Wnt3a plays a role in these processes:
Wnt3A patterns a multipotent stem cell population that form neurons, muscles, bones, and cartilage of the torso region. Wnt3a instructs these multipotent stems cells to form muscle, bone, and cartilage progenitors over forming neurons.[8] Wnt3A also regulates the Notch pathway to control the segmentation clock needed for normal torso development [9][10]
Left-Right patterning
[edit]Wnt3a is in a signaling pathway that activates the gene Nodal which is left side signaling determinant [11]
Intestine - Colon
[edit]The colon portion of the gastrointestinal tract is completely dependent on Wnt3a and Wnt3a selectively causes the growth of colon progenitors [12]
Neural crest
[edit]Wnt3a expands neural crest cells during early development [13]
Blood cells
[edit]Wnt3a promotes hematopoietic stem cell self-renewal. Wnt3a is needed for myeloid but not B-lymphoid development at the progenitor level, and affected immature thymocyte differentiation [14]
Brain - Hippocampus
[edit]Wnt3a is needed for formation of the hippocampus portion of the brain [15]
Teeth
[edit]Wnt3a promotes stem cell properties of dental pulp stem cells [16]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000154342 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000009900 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: WNT3A wingless-type MMTV integration site family, member 3A".
- ^ Yoshikawa Y, Fujimori T, McMahon AP, Takada S (March 1997). "Evidence that absence of Wnt-3a signaling promotes neuralization instead of paraxial mesoderm development in the mouse". Developmental Biology. 183 (2): 234–42. doi:10.1006/dbio.1997.8502. PMID 9126297.
- ^ Pashirzad M, Fiuji H, Khazei M, Moradi-Binabaj M, Ryzhikov M, Shabani M, et al. (October 2019). "Role of Wnt3a in the pathogenesis of cancer, current status and prospective". Molecular Biology Reports. 46 (5): 5609–5616. doi:10.1007/s11033-019-04895-4. PMID 31236761. S2CID 195329662.
- ^ Garriock RJ, Chalamalasetty RB, Kennedy MW, Canizales LC, Lewandoski M, Yamaguchi TP (May 2015). "Lineage tracing of neuromesodermal progenitors reveals novel Wnt-dependent roles in trunk progenitor cell maintenance and differentiation". Development. 142 (9): 1628–38. doi:10.1242/dev.111922. PMC 4419273. PMID 25922526.
- ^ Aulehla A, Wehrle C, Brand-Saberi B, Kemler R, Gossler A, Kanzler B, Herrmann BG (March 2003). "Wnt3a plays a major role in the segmentation clock controlling somitogenesis". Developmental Cell. 4 (3): 395–406. doi:10.1016/s1534-5807(03)00055-8. PMID 12636920.
- ^ Nakaya MA, Biris K, Tsukiyama T, Jaime S, Rawls JA, Yamaguchi TP (December 2005). "Wnt3a links left-right determination with segmentation and anteroposterior axis elongation". Development. 132 (24): 5425–36. doi:10.1242/dev.02149. PMC 1389788. PMID 16291790.
- ^ Nakaya MA, Biris K, Tsukiyama T, Jaime S, Rawls JA, Yamaguchi TP (December 2005). "Wnt3a links left-right determination with segmentation and anteroposterior axis elongation". Development. 132 (24): 5425–36. doi:10.1242/dev.02149. PMC 1389788. PMID 16291790.
- ^ Garriock RJ, Chalamalasetty RB, Zhu J, Kennedy MW, Kumar A, Mackem S, Yamaguchi TP (April 2020). "A dorsal-ventral gradient of Wnt3a/β-catenin signals controls mouse hindgut extension and colon formation". Development. 147 (8): dev185108. doi:10.1242/dev.185108. PMC 7174843. PMID 32156757.
- ^ Ikeya M, Lee SM, Johnson JE, McMahon AP, Takada S (October 1997). "Wnt signalling required for expansion of neural crest and CNS progenitors". Nature. 389 (6654): 966–70. Bibcode:1997Natur.389..966I. doi:10.1038/40146. PMID 9353119. S2CID 4359867.
- ^ Luis TC, Weerkamp F, Naber BA, Baert MR, de Haas EF, Nikolic T, et al. (January 2009). "Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation". Blood. 113 (3): 546–54. doi:10.1182/blood-2008-06-163774. hdl:1765/19345. PMID 18832654. S2CID 1932170.
- ^ Lee SM, Tole S, Grove E, McMahon AP (February 2000). "A local Wnt-3a signal is required for development of the mammalian hippocampus". Development. 127 (3): 457–67. doi:10.1242/dev.127.3.457. PMID 10631167.
- ^ Uribe-Etxebarria V, García-Gallastegui P, Pérez-Garrastachu M, Casado-Andrés M, Irastorza I, Unda F, et al. (March 2020). "Wnt-3a Induces Epigenetic Remodeling in Human Dental Pulp Stem Cells". Cells. 9 (3): E652. doi:10.3390/cells9030652. PMC 7140622. PMID 32156036.
Further reading
[edit]- Smolich BD, McMahon JA, McMahon AP, Papkoff J (December 1993). "Wnt family proteins are secreted and associated with the cell surface". Molecular Biology of the Cell. 4 (12): 1267–75. doi:10.1091/mbc.4.12.1267. PMC 275763. PMID 8167409.
- Huguet EL, McMahon JA, McMahon AP, Bicknell R, Harris AL (May 1994). "Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue". Cancer Research. 54 (10): 2615–21. PMID 8168088.
- Gazit A, Yaniv A, Bafico A, Pramila T, Igarashi M, Kitajewski J, Aaronson SA (October 1999). "Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response". Oncogene. 18 (44): 5959–66. doi:10.1038/sj.onc.1202985. PMID 10557084.
- Tanaka K, Okabayashi K, Asashima M, Perrimon N, Kadowaki T (July 2000). "The evolutionarily conserved porcupine gene family is involved in the processing of the Wnt family". European Journal of Biochemistry. 267 (13): 4300–11. doi:10.1046/j.1432-1033.2000.01478.x. PMID 10866835.
- Katoh M (February 2002). "Regulation of WNT3 and WNT3A mRNAs in human cancer cell lines NT2, MCF-7, and MKN45". International Journal of Oncology. 20 (2): 373–7. doi:10.3892/ijo.20.2.373. PMID 11788904.
- Katoh M (March 2002). "Molecular cloning and expression of mouse Wnt14, and structural comparison between mouse Wnt14-Wnt3a gene cluster and human WNT14-WNT3A gene cluster". International Journal of Molecular Medicine. 9 (3): 221–7. doi:10.3892/ijmm.9.3.221. PMID 11836627.
- Filali M, Cheng N, Abbott D, Leontiev V, Engelhardt JF (September 2002). "Wnt-3A/beta-catenin signaling induces transcription from the LEF-1 promoter". The Journal of Biological Chemistry. 277 (36): 33398–410. doi:10.1074/jbc.M107977200. PMID 12052822.
- Hering H, Sheng M (June 2002). "Direct interaction of Frizzled-1, -2, -4, and -7 with PDZ domains of PSD-95". FEBS Letters. 521 (1–3): 185–9. doi:10.1016/S0014-5793(02)02831-4. PMID 12067714. S2CID 39243103.
- Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Hino S, Michiue T, Asashima M, Kikuchi A (April 2003). "Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin". The Journal of Biological Chemistry. 278 (16): 14066–73. doi:10.1074/jbc.M213265200. PMID 12556519.
- Qiang YW, Endo Y, Rubin JS, Rudikoff S (March 2003). "Wnt signaling in B-cell neoplasia". Oncogene. 22 (10): 1536–45. doi:10.1038/sj.onc.1206239. PMID 12629517.
- Hocevar BA, Mou F, Rennolds JL, Morris SM, Cooper JA, Howe PH (June 2003). "Regulation of the Wnt signaling pathway by disabled-2 (Dab2)". The EMBO Journal. 22 (12): 3084–94. doi:10.1093/emboj/cdg286. PMC 162138. PMID 12805222.
- Liu G, Bafico A, Harris VK, Aaronson SA (August 2003). "A novel mechanism for Wnt activation of canonical signaling through the LRP6 receptor". Molecular and Cellular Biology. 23 (16): 5825–35. doi:10.1128/MCB.23.16.5825-5835.2003. PMC 166321. PMID 12897152.
- Swiatek W, Tsai IC, Klimowski L, Pepler A, Barnette J, Yost HJ, Virshup DM (March 2004). "Regulation of casein kinase I epsilon activity by Wnt signaling". The Journal of Biological Chemistry. 279 (13): 13011–7. doi:10.1074/jbc.M304682200. PMID 14722104.
- Zilberberg A, Yaniv A, Gazit A (April 2004). "The low density lipoprotein receptor-1, LRP1, interacts with the human frizzled-1 (HFz1) and down-regulates the canonical Wnt signaling pathway". The Journal of Biological Chemistry. 279 (17): 17535–42. doi:10.1074/jbc.M311292200. PMID 14739301.
- Lu W, Yamamoto V, Ortega B, Baltimore D (October 2004). "Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth". Cell. 119 (1): 97–108. doi:10.1016/j.cell.2004.09.019. PMID 15454084. S2CID 18567677.
- Capurro MI, Shi W, Sandal S, Filmus J (December 2005). "Processing by convertases is not required for glypican-3-induced stimulation of hepatocellular carcinoma growth". The Journal of Biological Chemistry. 280 (50): 41201–6. doi:10.1074/jbc.M507004200. PMID 16227623.
- Thrasivoulou C, Millar M, Ahmed A (December 2013). "Activation of intracellular calcium by multiple Wnt ligands and translocation of β-catenin into the nucleus: a convergent model of Wnt/Ca2+ and Wnt/β-catenin pathways". The Journal of Biological Chemistry. 288 (50): 35651–9. doi:10.1074/jbc.M112.437913. PMC 3861617. PMID 24158438.
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