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Abstract

Diverse shapes and patterns observed in nature are the optimal representation for fulfilling an organism's physiological needs and function, and they follow a shared set of design principles. Understanding how an organ acquires its functional form requires the reconstruction of its developmental trajectory, which bridges macroscopic tissue geometry to cellular behaviors. However, the inherent complexity on both scales presents challenges for 3D characterization. The field is in search of a 3D model organ that connects the complex morphogenetic and regulatory processes on different scales while reducing the complexity to draw general principles. In this thesis, I use Drosophila pupal retina as the simplest complex 3D model to explore basic rules of organ morphogenesis. To establish a comprehensive framework, I develop three assays to characterize developmental trajectories on three different scales. On the macroscopic tissue scale, I use microCT to quantitatively describe retinal 3D geometrical changes that establish the precise optical alignment. The tissue analysis revealed two distinct phases of retinal geometrical transformation and suggested that retina establishes the proper optical alignment prior to the significant growth phase. On the mesoscale, considering each ommatidium as a multicellular unit, I develop a machine-learning based pipeline that provides a coarse-grained description of ommatidial packing across the retinal epithelium. The initial coordination of the apical and basal patterning affects the subsequent growth pattern and the final tissue morphology. On the cellular scale, I use confocal microscopy and 3D reconstruction to examine the cellular basis underlying the tissue growth pattern. I uncover a feedback mechanism between the pigment cells and photoreceptors that spatially coordinates the morphogenetic processes during retinal growth.Together, this thesis provides a multiscale framework to study 3D retinal morphogenesis. I suggest that the basic principles identified in the retinal context will be at the core of other complex 3D morphogenetic programs.

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