Knockdown of Atg1 Impairs Brain Regeneration and Downregulates ECM-Related Genes in the Planarian Dugesia japonica.

Planarian regeneration is a complex process that involves the precise orchestration of cell proliferation, differentiation, migration, and autophagy. However, the role of autophagy in planarian regeneration remains poorly understood. In this study, we identified autophagy-related gene 1 from the planarian Dugesia japonica (designated as DjAtg1) and investigated its role in planarian brain regeneration. DjAtg1 transcripts are highly expressed in the cephalic ganglia of intact planarians. Following amputation, DjAtg1 is prominently expressed in the newly regenerated brain tissues. Knockdown of DjAtg1 via RNA interference (RNAi) induces head regression, with all RNAi-treated animals regenerating a small triangular-shaped head. Neoblast-marker labeling experiments demonstrate that DjAtg1 knockdown does not affect cell proliferation but impairs neoblast behavior. Notably, RNA-seq reveals that most of these down-regulated transcripts are linked to the extracellular matrix (ECM). Based on our findings and prior literature, we propose that the DjAtg1-mediated secretory pathway is essential for ECM remodeling. DjAtg1 knockdown disrupts the secretory pathway, which feedback-inhibits the expression of ECM-related genes. Our work provides new insights into the non-canonical role of autophagy in regulating of ECM remodeling during planarian regeneration.