Loss of GPC6 drives pathological ERK activation in developing bone — without any mutation in the RAS–MAPK pathway. pERK signal (green) is markedly elevated in GPC6 KO compared to wildtype. A RASopathy-like state from a WNT gradient defect 🤯 #RASopathy #ERK #WNT5A"

Source-proximal WNT5A hyperactivation has a completely unexpected consequence — it engages a previously unrecognised WNT5A–RAC–PAK–MEK–ERK cascade, driving pathological ERK activation in developing bone without any mutation in the conventional RAS–MAPK pathway. #RASopathy #ERK #WNT5A

WNT5A forms a gradient across the growth plate. Loss of GPC6 collapses it — WNT5A is consumed at its source, hyperactivating local signalling while depriving distal tissue of ligand! The same tissue experiences both gain and loss of signalling 🤯 GPC6 is a spatial allocator of WNT5A. #WNT5A #GPC6