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Abstract

At its core, developmental biology can be reduced to the study of three overarching processes; axiation, pattern formation and induction. By exploiting the formation of the lateral line system during embryogenesis in Medaka fish, I was able to contribute novel insights to each of these fundamental processes. The lateral line system is a sensory module present in fish and amphibians and is composed of individual neuromast organs. Its main function is to sense the direction of water flow and relay the information back to the brain. A fantastic diversity of lateral line patterns exists in the wild, the basis of which remains largely unknown. By live- imaging the polarized migration (axiation) of tissue during development I was able to demonstrate how the formation of the posterior lateral line in Medaka fish occurs. This led to a reassessment of the prevailing view held in the field, as it for the first-time placed changes in pattern construction occurring during development as a major contributor to the diversity of lateral line patterns. It also led to the discovery that the same molecular players can result in the formation of different posterior lateral line patterns in different teleost species, simply by modulating their temporal and spatial expression profiles. This modulation has been repeatedly spotted by developmental biologists studying a variety of organisms, and thus can be regarded as a common principle driving evolutionary novelty.

Using a variety of available and newly generated mutants I delved deeper into the guiding logic/principles behind posterior lateral line pattern formation. A process revealed to harbour a high degree of plasticity and self-organization. Specifically, I was able to show that precursor clusters of the migrating primordium can act as autonomous units, demonstrating the plasticity of the developmental tissue of origin for neuromasts (the primordium). In fact, within the same animal the left and right posterior lateral lines have varying outputs, reinforcing the idea of an inherent plasticity of primordia and strongly suggesting the presence of a low- range Waddingtonian developmental buffering system. Along the same lines, I was able to show that changes in the immediate environment surrounding the primordium (for e.g. epithelial morphology) can have a direct effect on the posterior lateral line pattern being formed. And postulate that these properties of the system might have constituted a fault-line that evolution could have exploited to generate the kaleidoscopic variety of lateral line patterns we observe in the wild. Going from tissue level dynamics to individual organs, I focus on the differentiation of neuromasts and provide strong evidence for the location and potency of the stem cells that maintain them. I also report that during development neural stem cell precursors induce the formation of their own niches, which in turn are used to maintain the stem cells life-long. A finding that could have important implications in fields like tissue engineering and stem cell biology. Lastly, I focused my efforts on the cellular level by studying the post-embryonic formation of neuromasts, a process that re-utilizes axiation, is highly stereotypical and driven by individual cell behaviour. I characterize in detail the cells participating in post-embryonic organogenesis and reveal early molecular heterogeneities within the stem cells that seem to contribute to the differential behaviour they undergo later on. All in all, traversing tissue to organ and finally cellular scales in the lateral line led to novel insights into how this system is built and maintained all whilst being constantly remodelled. Surprisingly this approach even led to initial insights on the evolution of lateral lines. As with the nature of all scientific progress no matter how miniscule, more questions have been conjured that need to be answered in due time.