Src acts with WNT/FGFRL signaling to pattern the planarian anteroposterior axis

Abstract

Tissue identity determination is critical for regeneration, and the planarian anteroposterior (AP) axis uses positional control genes expressed from bodywall muscle to determine body regionalization. Canonical Wnt signaling establishes anterior versus posterior pole identities through notum and wnt1 signaling, and two Wnt/FGFRL signaling pathways control head and trunk domains, but their downstream signaling mechanisms are not fully understood. Here we identify a planarian Src homolog that restricts head and trunk identities to anterior positions. src-1(RNAi) animals formed enlarged brains and ectopic eyes and also duplicated trunk tissue, similar to a combination of Wnt/FGFRL RNAi phenotypes. src-1 was required for establishing territories of positional control gene expression, indicating it acts at an upstream step in patterning the AP axis. Double RNAi experiments and eye regeneration assays suggest src-1 can act in parallel to at least some Wnt and FGFRL factors. Co-inhibition of src-1 with other posterior-promoting factors led to dramatic patterning changes and a reprogramming of Wnt/FGFRLs into controlling new positional outputs. These results identify src-1 as a factor that promotes robustness of the AP positional system that instructs appropriate regeneration. HighlightsO_LISrc-1 suppresses head and trunk identity C_LIO_LISrc-1 can regulate positional control gene domains C_LIO_LISrc-1 likely acts independently of notum/Wnt and FGFRL signals C_LIO_LISrc-1 inhibition broadly sensitizes animals to AP pattern disruption C_LI