Growth and Scaling during Development and Regeneration

Abstract

Life presents fascinating examples of self-organization and emergent phenomena. In multi-cellular organisms, a multitude of cells interact to form and maintain highly complex body plans of well-defined size. In this thesis, we investigate theoretical feedback mechanisms for both self-organized body plan patterning and size control. The thesis is inspired by the astonishing scaling and regeneration abilities of flatworms. These worms can perfectly regrow their entire body plan even from tiny amputation fragments like the tip of the tail. Moreover, they can grow and actively de-grow by more than a factor of 40 in length depending on feeding conditions. These capabilities prompt for remarkable physical mechanisms of self-organized pattern formation and scaling. First, we explore the basic principles and challenges of pattern scaling in mechanisms previously proposed to describe biological pattern formation. Next, we present a novel class of patterning mechanisms yielding entirely self-organized and self-scaling patterns. This framework captures essential features of body plan regeneration and scaling in flatworms. Further, we analyze shape and motility of flatworms. By applying principal component analysis, we characterize shape dynamics during different motility modes and also identify shape variations between different flatworm species. Finally, we investigate the metabolic control of cell turnover and growth. We identify three mechanisms of metabolic energy storage; theoretical descriptions thereof can explain the measured organism growth by rules on the cellular scale. In a close collaboration with experimental biologists, we combine minimal theoretical descriptions with state-of-the-art experiments and data analysis. This allows us to identify generic principles of scalable body plan patterning and growth control in flatworms.