Understanding the mechanisms that govern organ morphostasis and repair
Neuromasts are the sensory organs used by fishes and amphibians to sense water displacement. Neuromasts contain hair cells that are very similar to our own inner ear cells. Unlike mammalian ear cells, bird and fish hair cells regenerate after ablated. Understanding the mechanisms responsible for the development and regeneration of the sensory organs holds the promise of treating deafness in humans.  The study of neuromasts is also of advantage for basic science. With its three cell types, and 70 cells total, neuromasts are a relatively simple organ. They provide a good model to investigate unanswered questions about organogenesis: What makes cells proliferate during organ regeneration or development? What signals them to stop after normal organ size and cell number is reached? How is organ architecture – shape, cell placement, orientation– attained? Is it an intrinsic property of the interactions between its components (self-organization) or does it depend on external cues?  I will establish a system for the production of neuromast organoids in vitro. This will serve to interrogate the role of self-organization in the process of tissue repair. I will also use a combination of single cell transcriptomics, fluorescence marker imaging, gene editing and pharmacological treatments to collect multidimensional data from cells during neuromast regeneration. The use of unbiased computational techniques derived from machine learning will help us untangle the molecular and cellular players driving cellular organization in this system.