NR1I3 modulates Wnt signaling to promote anterior-posterior axis patterning.

Abstract

Background: Regeneration of missing structures and tissue turnover during homeostasis require positional information to instruct the reestablishment of body axes and to specify new cells to replace aged tissues. Planarians present an ideal model for positional information studies, as they can regenerate any missing parts and replace aged cells during tissue turnover. Position control genes (PCGs) characterized by constitutive and regional expression in planarians have been identified to instruct regeneration and tissue turnover. However, it is not entirely understood how these genes coordinate in maintaining proper tissue structures.

Results: Here we report that NR1I3, a nuclear receptor family transcription factor, functions in the establishment and maintenance of the anteroposterior (AP) axis in planarians. NR1I3 RNA interference (RNAi) during regeneration caused ectopic head formation in the posterior blastema, correlated with symmetric notum expression at wounds. Loss of NR1I3 function in intact planarians resulted in ectopic anterior eye formation and the absence or reduction of posterior PCG expression. Notably, the phenotype of two-headed planarians after NR1I3 RNAi can be suppressed by APC, axins, and notum, which are components of the Wnt signaling.

Conclusions: Our data reveal that NR1I3 in planarians acts as an upstream regulator of Wnt signaling, mediating AP patterning through regulating the activation of notum.