Analysis of the Regulation of  Stem Cells Controlling Planarian Regeneration and Scaling

Schad, Erik Gregory

doi:https://doi.org/10.21985/n2-zdc2-7c54

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Analysis of the Regulation of Stem Cells Controlling Planarian Regeneration and Scaling

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Animals must establish the correct form during development. Regeneration is a process by which some animals reestablish their form following injury. This process requires both the generation of new missing cells after injury, and information to pattern new cells to reestablish the correct form. Planarian flatworms have an almost unlimited capacity to regenerate missing tissues. Understanding how planarians produce and pattern new tissues may illuminate mechanisms of regeneration as well as the establishment of form across animals. In this thesis I present evidence that the regulation of stem cells is important for both the production of new tissues, but almost the regulation of form during regeneration. I used high throughput RNAi screening and qPCR technologies to uncover stem cell regulators. We screened hundreds of kinases and other signaling molecules for regeneration defects, and then examined the expression of stem cell and progenitor cell type markers using high-throughput qPCR. I show that 17 genes were required for broad maintenance of stem cells. I show that mink1 is required for stem cell differentiation, adenylate kinase 2 was required for the specification of intestine cell progenitors, and map4k-3, pak-1, and mob4 all were negative regulators of stem cell marker expression. Additionally, I show that mob4 is an important factor limiting total size through the restriction of posterior tissue. Taken together, these findings provide evidence that regulation of stem cells are required for both the production of new cells during regeneration, but also the establishment of correct tissue proportionality.

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