Loss of GPC6 generates a molecular hybrid of 2 developmental diseases: WNT5A deficiency characteristic of Robinow syndrome and pathological ERK activation characteristic of the RASopathies. Omodysplasia caused by loss of GPC6 overlaps both disease classes. #omodysplasia #RASopathy #Robinow

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

Proud to share the labs first preprint! Led by Yeon, whose hard work, dedication and drive have been instrumental in bringing the project to this point. Thank you to everyone involved, especially long-term collaborators Yvonne and Yuguang. #Wnt #WntUK #RASopathy #ERK

www.biorxiv.org/content/10.6...