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. 2018 Nov 29;247(1):86–98. doi: 10.1002/path.5171

Figure 6.

PATH-5171-FIG-0006-c

WNT5A is a likely differentiation‐promoting agent in Wilms tumour. WNT5A detected by IHC in WiT49‐based IRX3 and IRX5 knockout xenografts (A–F). Arrows point at WNT5A‐positive tumour tubules. Short arrows point at WNT5A‐negative stroma cells. Areas magnified ×3 of WNT5A‐negative stroma cells are inserted in (B) and (E). WNT5A expression in human foetal kidney at gestational week (gw) 10 and Wilms tumour (G and H, respectively). Arrowhead points at WNT5A‐positive stroma. Arrow with open arrowhead points at WNT5A‐positive metanephric mesenchyme. Arrows with filled arrowheads denote primitive nephrogenic elements. The insertion in H is a ×2 magnification of tumour tubules (H). Scale bars correspond to 100 μm. S = stroma. B = blastema. All immunostains are brown. (I) Cartoon depicting the proposed interplay between IRX3, IRX5 and WNT5A in nephrogenesis. IRX5 acts together with canonical/WNT‐β catenin signalling and disturbed Hippo signalling to maintain proliferative nephrogenesis. Polarisation and elongation are obtained via the integration of active Hippo and non‐canonical WNT signalling, where IRX3 and WNT5A, via stimulation of ALCAM, are crucial. Disturbed IRX3 and IRX5 expression, epitomised by Wilms tumour, inhibits MET and polarisation of immature mesenchyme. According to our model, exogenous WNT5A could potentially override the differentiation block present in Wilms tumour.