Role of cytoplasmic poly (A) binding protein during planaria regeneration

Identifying the cellular events that facilitate stem cell function and tissue organization is critical for understanding the process of regeneration. Planaria because of their robust regeneration and the presence of pluripotent stem cells known as neoblast, have emerged as a powerful model system to study stem cell biology and regeneration. Here using planaria as a model system, we show that the initial events essential for wound healing such as epithelialization and organization of epidermis is critical for the neoblast function. We also identified an RNA binding protein, Poly A binding protein Cytoplasmic, SMED-PABPC2, which is essential for epithelialization and epidermal organization during planarian regeneration. knockdown (KD) of Smed-pabpc2 lead to defects in epidermal migration, disorganization of epidermis and ECM, which unexpectedly lead to a selective failure in the localized proliferation of neoblast near the wound region. In planarians, sub-epidermal layer is attached to epidermal layer via ECM. Though smed-pabpc2 KD animals showed disorganization of epidermis and ECM, no gross defects were observed in the sub-epidermal muscle layer organization. However, we observed drastic decrease in the expression of positional control genes (PCGs) expressed in this layer, which provide positional cues for neoblast differentiation. We also identified epidermal lineage transcripts such as zfp-1 to be translationally regulated by pabpc2 giving a mechanistic insight into the role of PABPC2. Together, our results uncover a novel role of SMED- PABPC2 in the maintenance of epidermal and ECM integrity, which is important for the spatial control of neoblast function in the context of regeneration.