There is an unbreakable link between shape and function. In biology, the architecture of cells, tissues and organisms, that have evolved adapting to the world around them, translate into specific functional outcomes. Self-organization is an adaptive, non-linear and dynamic process, where diverse ordered patterns emerge from an initially disordered and noisy state through local interactions between the elements of a system. This can lead to the fascinating biological diversity and functional complexity in such systems. Unwavering storms on the surface of Jupiter, patterns on the wing of a butterfly, a regenerating planarian eye, development of a neuronal circuit in the human brain can all be studied systematically using the conceptual tools derived from the field of self-organization. Here, I sought to address a central, but understudied, problem in animal regeneration: How do regenerative progenitors organize into complex replacement structures in the context of adult anatomy? I used the planarians as a system for studying regenerative progenitors and focused on eye regeneration to elucidate the mechanisms. I found that selforganization has a major role in determining the behavior of regenerative progenitors. This work revealed three properties that govern regenerative progenitor behavior, and these three properties in concert explain many previously mysterious aspects of how regeneration works: (i) selforganization, (ii) an extrinsic migratory target for progenitors, and (iii) a broad progenitor specification zone that allows progenitors to be targeted into self-organizing systems even if they are transiently in incorrect locations during the process of regeneration. These components yield a model with broad explanatory and predictive power. As an example, we were able to generate wild-type animals with 3, 4, or 5 eyes instead of 2 by simple manipulations of the system using the model developed. Remarkably, the extra eyes were stably maintained throughout the life of the animal, resulting in wild-type animals with an alternative and stable anatomical state. This model prominently incorporates self-organizing principles, which have been little explored in regeneration. The new conceptual model with broad explanatory power allowed us to address some of the fundamental pervious mysteries of regeneration.

https://www.dropbox.com/s/ibzlzej7z8m925z/KDAtabay_Thesis_Final.pdf?dl=0