Overactivation of the Wnt signalling pathway is well known to be associated with colo-rectal cancer, and the role of Wnt in regulating intestinal stem cell activity has been intensely studied. However, less is understood about the potential functions of this pathway during colon development. Terry Yamaguchi and colleagues use knockout, overexpression and lineage-tracing approaches to investigate the role of the Wnt3a ligand in hindgut formation. In the posterior embryo, Wnt3a is expressed in a dorsal-ventral gradient across all germ layers; known Wnt3a targets can be detected in the dorsal, but not ventral, hindgut. In wild-type embryos, the hindgut endoderm extends as the axis elongates, but upon knockout of Wnt3a, this does not happen – the hindgut can be specified, but its subsequent growth is severely impaired. Conversely, overactivation of the pathway leads to overgrowth of the colon during development. The authors further demonstrate that proper hindgut development requires active Wnt signalling in the dorsal region but silencing of the pathway in the ventral tissue. They propose that the dorsal hindgut may act as a signalling centre, with Wnt3a regulating the expression of another signal – perhaps Bmp - that acts on the ventral hindgut to coordinate growth of the colon.
Wnt3a: coordinating colon development
Wnt3a: coordinating colon development. Development 15 April 2020; 147 (8): e0802. doi:
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