Autonomous and non-autonomous regulation fo planarian growth and regeneration"Smed-bls", canonical Wnt signaling and Fox family

Resumen

Development requires an increment of cell growth and cell number. Cell communication enables spatiotemporal patterning to acquire all the cell fate. Planarians are a unique model to study development since their ability to regenerate and modulate body size accordingly to the nutrient availability. This body plasticity is based on the presence of pluripotent adult stem cells (neoblasts). The balance between cell proliferation and cell death define cell number and planarian body size. blitzschnell is a family formed of de novo and taxonomically restricted genes that control cell number trough cell proliferation and cell death. Planarians are able to proportionate their organs to the according size. This regulation is mediated by different signalling centres that specify regions trough the 3 main axes. After amputation, the anterior and posterior tips behave as organizers (signalling centres), being defined by notum (Wnt inhibitor) and wnt1 expression, respectively. The inhibition of any of those elements leads to a shift in polarity. To decipher the molecular interactions that regulate the expression of wnt1 to the posterior tip and confer the organizing activity we used genome wide approaches. ATAC-seq and RNA-seq analysis of regenerating wild-type and wnt1 (RNAi) planarians allowed the identification of specific Cis-Regulatory Elements (CREs) of posterior regeneration. At 12 hours of regeneration, the accessible CREs in posterior blastemas have essentially changed, indicating that specific posterior chromatin changes induced by amputation occur much earlier than the formation of the organizers. Furthermore, we have identified specific transcription factors (TF) enriched in posterior CREs and are essential for the specification of the posterior organizer. TFs regulate patterning events and developmental specification, particularly Fox Family exerts crucial role defining cell types or regulating cell cycle. Poorly is known about their presence in Schmidtea mediterranea (Smed) neither the Lophocotrozoan clade. We investigate the Fox family evolution this clade We identified Fox genes in Smed, characterizing the sequence, expression and function. Overall, we studied different mechanisms that regulate growth and regeneration, and how they are integrated in the plastic planarian.