Cell Signaling and Pattern Control in Tissue Remodeling and RegenerationPublic Deposited
Regeneration is a complex biological phenomenon. Organisms that regenerate must possess robust mechanisms that direct new tissue production of the appropriate size and pattern to allow for correct and functional integration with preexisting tissue structures. Planarians are flatworms capable of regenerating from nearly any injury, making them a powerful system for the study of pattern and size control during regeneration. In this thesis, I present evidence that the spatial expression of signaling molecules can direct the regeneration and maintenance of appropriate body form. I identify a negative feedback loop of spatially secreted Wnt signaling factors within the brain that acts to regulate appropriate organ size in all regenerative contexts. This feedback loop likely controls the reversible growth of the brain through the regulation of stem cell differentiation. Additionally, I show that secreted factors expressed from the animal poles during regeneration and maintenance can affect tissue pattern at a distance and upstream of regional patterning circuits. Furthermore, I find that tissue maintenance can occur independent of body-wide pattern and propose that mature organs may possess autonomous mechanisms to influence the incorporation of new cells. Together, these findings provide new insight into the regulatory logic and molecular mechanisms that can allow for the restoration of positional information and ultimate regeneration of animal form.
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