Kishore Rao Mosaliganti

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  Inner ear size and shape is regulated by pressure, transport, and tissue mechanics
  Kishore Rao Mosaliganti

  How do animals develop similar organ sizes and shapes despite large fluctuations in initial growth conditions? How is size and shape control achieved across molecular-cellular-tissue scales? We answer this question in the context of early ear development that exhibits a highly stereotyped pattern of assembly and growth. Using in toto imaging technologies in the zebrafish embryo, we reconstructed morphogenetic patterns of cellular movements, cell number and shape changes, and tissue topology changes. We show that otic vesicle growth and regeneration is characterized by endolymph pressure and tissue stretching forces that provide feedback to circuits responsible for generating endolymph fluid. To systematically investigate how otic vesicle growth is controlled, we developed a minimal mathematical model linking tissue geometry and mechanics to tissue stretching forces, thus illuminating how size control to stage-specific volumes is accomplished. Because ear development shares many features with other developmental (eye, heart, kidney) and disease processes (tissue tumor formation), our results and mathematical model will inform understanding of the morphogenesis of other organs.