Long-range Coordination of Biochemical Signals in Drosophila Embryogenesis and Zebrafish Scale Regeneration

Abstract

Coordination of biochemical signals across long distances is a ubiquitous feature of biological systems; however, the molecular and mechanical mechanisms which allow such signaling are still largely unknown. I discuss general classes of long-range signaling mechanisms as well as the regulatory pathways involved in creating and maintaining cellular coordination in different size scales. In particular, I present a thorough mathematical analysis of a reaction-diffusion model of Erk activity waves which control osteoblast regeneration in the zebrafish scale and use live and fixed imaging of Drosophila melanogaster embryos to elucidate the mechanisms of synchronized cell cycle control. In the regenerating zebrafish scale, I show that a simple three-component model consisting of Erk, an Erk activator, and an Erk inhibitor is sufficient to generate Erk activity waves which propagate across the millimeter sized region. The properties of these waves agree with chemical wave theory and are structured to enable proper timing of hypertrophy to enable precise regulation of size and shape of the regenerated tissue. In the early Drosophila embryo, I show that the ubiquitin ligase Cullin-5 acts to regulate the actin cytoskeleton. Using novel mutants, I show that mutations in the cullin-5 gene leads to a disruption in signaling across the embryo and an eventual mistiming of the mid-blastula transition. Furthermore, I show that the cell cycle is not controlled globally across the embryo or very locally but rather is coordinated across distances of ~100µm. This work highlights the different mechanisms and regulation which exists in different contexts to transmit signals across a domain and control the proper development and regeneration of large tissues.