Wikipedia

WNT3A

Protein Wnt-3a is a protein that in humans is encoded by the WNT3A gene.[5]

WNT3A
Identifiers
AliasesWNT3A, Wnt family member 3A
External IDsOMIM: 606359; MGI: 98956; HomoloGene: 22528; GeneCards: WNT3A; OMA:WNT3A - orthologs
Orthologs
SpeciesHumanMouse
Entrez

89780

22416

Ensembl

ENSG00000154342

ENSMUSG00000009900

UniProt

P56704

P27467

RefSeq (mRNA)

NM_033131

NM_009522

RefSeq (protein)

NP_149122

NP_033548

Location (UCSC)Chr 1: 228.01 – 228.06 MbChr 11: 59.14 – 59.18 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.

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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

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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

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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:

Body plan - Torso

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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

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Wnt3a is in a signaling pathway that activates the gene Nodal which is left side signaling determinant [11]

Intestine - Colon

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The colon portion of the gastrointestinal tract is completely dependent on Wnt3a and Wnt3a selectively causes the growth of colon progenitors [12]

Neural crest

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Wnt3a expands neural crest cells during early development [13]

Blood cells

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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

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Wnt3a is needed for formation of the hippocampus portion of the brain [15]

Teeth

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Wnt3a promotes stem cell properties of dental pulp stem cells [16]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000154342 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000009900 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: WNT3A wingless-type MMTV integration site family, member 3A".
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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

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