DjFNDC3A is associated with DjSmad4 to regulate cranial nerve regeneration in planarian (Dugesia japonica).

FNDC3A protein, widely expressed in various tissues, is involved in a variety of biological processes, such as, tail bud development and caudal fin regeneration in zebrafish. However, functional studies of FNDC3A in planarians have not been reported. In this study, we examined the spatiotemporal expression pattern of DjFNDC3A and investigated its functions in planarians regeneration. Knockdown of DjFNDC3A resulted in severe defects, including poorly defined brain lobes, complete loss of brain lateral branches and reduction of multiple neuronal populations. Silencing DjFNDC3A did not affect the neoblast marker PiwiA+ cells, suggesting that knockdown of DjFNDC3A did not affect neoblast in the regenerative planarians. To further investigate the mechanisms underlying the defective nerve regeneration, RNA-seq analysis was performed to identify transcriptomic alterations upon DjFNDC3A RNAi. Smad4 was significantly down-regulated in response to DjFNDC3A RNAi. Knockdown of DjSmad4 similarly resulted in a marked reduction of dopaminergic (DA) neurons, resembling the defects observed in DjFNDC3A RNAi. These findings suggest DjFNDC3A is associated with DjSmad4 to regulate cranial nerve regeneration in planarian.