Back

Weckle is a molecular switch that diverts Toll signalling from innate immunity towards growth by engaging Yki

Perez-Sanchez, M. D.; Li, G.; Moncrieffe, M.; Rojo-Cortes, F.; Malinovska, K.; Sample, E.; Maddick, M.; Moreira, M.; Connolly, E. C.; Parsons, A.; Feuda, R.; Gay, N. J.; Hidalgo, A.

2026-02-20 developmental biology
10.64898/2026.02.18.706625 bioRxiv
Show abstract

The mechanisms underlying how the brain can switch from a plastic to a degenerative state are unknown. Tolls and Toll-Like receptors (TLRs) could be involved since they underlie both neuroinflammation and structural brain plasticity. Here, we show that the Toll signalling adaptor Weckle (Wek) - a ZAD-Zinc-finger transcription factor - can switch the response from promoting innate immunity or cell death, to inducing growth instead. Myristoylated Wek binds Tolls at the membrane, and concerted PI3K and Toll signalling drive its nuclear translocation. Wek interacts with Yorkie (Yki) - the key regulator of growth restrained by Hippo - enabling its nuclear shuttling. Remarkably, Wek blocks innate immunity. Instead, Wek and Yki together drive glial cell proliferation and growth. Through this mechanism, Toll signalling could promote structural brain plasticity via Wek and Yki downstream. As Tolls and Yki are widespread, these findings could have important implications for understanding also regeneration and cancer.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.