Abstract
Despite the intrinsically stochastic nature of damage, sensory organs recapitulate normal architecture during repair to maintain function. Here we present a quantitative approach that combines live cell-lineage tracing and multifactorial classification by machine learning to reveal how cell identity and localization are coordinated during organ regeneration. We use the superficial neuromasts in larval zebrafish, which contain three cell classes organized in radial symmetry and a single planar-polarity axis. Visualization of cell-fate transitions at high temporal resolution shows that neuromasts regenerate isotropically to recover geometric order, proportions and polarity with exceptional accuracy. We identify mediolateral position within the growing tissue as the best predictor of cell-fate acquisition. We propose a self-regulatory mechanism that guides the regenerative process to identical outcome with minimal extrinsic information. The integrated approach that we have developed is simple and broadly applicable, and should help define predictive signatures of cellular behavior during the construction of complex tissues.
Highlights
Understanding organogenesis, organ morphostasis and regeneration is crucial to many areas of biology and medicine, including controlled organ engineering for clinical applications (Lancaster et al, 2013; Boj et al, 2015; Sato and Clevers, 2015; Willyard, 2015)
Previous studies have extensively characterized the regeneration of the mechanosensory hair cells (Williams and Holder, 2000; Harris et al, 2003; Lopez-Schier and Hudspeth, 2006; Hernandez et al, 2006; Ma et al, 2008; Behra et al, 2009; Faucherre et al, 2009; Wibowo et al, 2011; Namdaran et al, 2012; Steiner et al, 2014; Jiang et al, 2014)
To obtain quantitative data of whole sensory-organ regeneration we developed an experimental assay that combines controllable neuromast damage, long-term videomicroscopy at cellular resolution, and live cell-lineage tracing
Summary
Understanding organogenesis, organ morphostasis and regeneration is crucial to many areas of biology and medicine, including controlled organ engineering for clinical applications (Lancaster et al, 2013; Boj et al, 2015; Sato and Clevers, 2015; Willyard, 2015). Structural reproducibility depends on the re-establishment of cell identity, number, localization and polarization. What is the mechanism that controls the correct reproduction of cell number and localization. The neuromasts are ideally suited for this purpose because they are small and external, facilitating physical access and three-dimensional high-resolution videomicroscopy of every cell during extended periods. Our comprehensive approach is simple and model independent, which should facilitate its application to other organs or experimental systems that are accessible to videomicroscopy. It should help reveal the basic rules that underlie how complex structures emerge from the collective behavior of cells
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