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Tissue Assembly and Pattern Control in Planarian Brain Regeneration

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Many human diseases are chronic and ultimately fatal because they damage organs and tissues beyond the body’s normal repair mechanisms. Therefore, there is significant medical interest in developing pharmaceuticals that enhance the body’s natural injury repair mechanisms and engineering organs in the lab for transplantation. However, comparatively little is known about the mechanism that govern regeneration in adult organisms. Planarians are flatworms famous for their ability to regenerate any missing body part after injury, making them a powerful model system for the study of adult tissue regeneration. Organ regeneration in planaria broadly requires three processes; stem cell specification into lineage specific progenitors, progenitor migration to target zones and organization of differentiating cells into 3D tissue assemblies. The finding I present here identity a function for src-1 as a global patterning regulator and suppressor of anterior identities. Further, I show that src-1 can regulate the regional identity and placement of progenitor target zones. In addition, I identify a previously unknown function for β1-integrin as a regulator of brain assembly during regeneration, independent of patterning. Notably, these results indicate that global pattern regulation and an abundant population of progenitors are not alone sufficient for the regeneration of complex tissue and organs such as the brain. Together, these findings provide new insights into the mechanisms that control tissue assembly and pattern regulation during planarian regeneration. Thus, this work has the potential to inform future strategies, to enhance both natural repair mechanisms and synthetic organ engineering.

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