Developmental Signals - Wnt

Introduction

A secreted glycoprotein patterning switch with different roles in different tissues and signaling has generally been divided into the canonical and non-canonical pathways. The name was derived from two drosophila phenotypes wingless and int and the gene was first defined as a protooncogene, int1. Humans have 19 identified members, with the major subgroup of Wnts (WNT1, WNT3A, WNT8) signaling through activation of beta-catenin dependent transcription from at least 4 WNT genes encoding secreted glycoproteins. At least one wnt receptor called frizzled (FZD). Wnt7a is secreted protein and binds to extracellular matrix. The mechanism of Wnt distribution (free diffusion, restricted diffusion and active transport) and all its possible cell receptors are still being determined. In the gastrointestinal system, Wnt maintains the pool of undifferentiated intestinal progenitor cells and control maturation and correct positioning of the Paneth cell (a differentiated intestinal cell type).

If you are interested in this family of proteins, look also at Roel Nusse -The Wnt Homepage.

Signaling Pathway

At least 3 separate signaling pathways have been identified in relation to Wnt singnaling.

1. Canonical pathway
2. Non-canonical or planar cell polarity pathway
3. Wnt-Calcium ion pathway

Canonical Pathway

1. Wnt binds the surface receptor Frizzled (Fz) and LRP5/6 receptor complex
2. Induces the stabilization of beta-catenin (through the DIX and PDZ domains of Dishevelled and other factors including Axin, glycogen synthase kinase 3 and casein kinase 1)
3. Beta-catenin translocates into the nucleus
4. Beta-catenin complexes with members of the LEF/TCF family of transcription factors.
5. Transcriptional induction of target genes.
6. Beta-catenin is then exported from the nucleus and degraded via the proteosomal machinery.

Non-Canonical Pathway

(Planar Cell Polarity Pathway)

1. Wnt binds the surface receptor Frizzled (Fz) independent of the LRP5/6 receptor complex.
2. Acts through Dishevelled (PDZ and DEP domains)
3. Mediates cytoskeletal (microfilament) changes through activation of the small GTPases Rho and Rac.

Wnt-Calcium Ion Pathway

1. Wnt binds the surface receptor Frizzled (Fz) and mediates activation of heterotrimeric G-proteins.
2. Acts internally through Dsh, phospholipase C, calcium-calmodulin kinase 2 (CamK2) and protein kinase C (PKC).
3. has various cellular functions including cell adhesion and motility.

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Cite this page: Hill, M.A. (2024, May 19) Embryology Developmental Signals - Wnt. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_Wnt

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G