Distinct progenitor populations mediate regeneration in the zebrafish lateral line.

David W Raible,Eric D Thomas

doi:10.7554/elife.43736

Abstract

Mechanosensory hair cells of the zebrafish lateral line regenerate rapidly following damage. These renewed hair cells arise from the proliferation of surrounding support cells, which undergo symmetric division to produce two hair cell daughters. Given the continued regenerative capacity of the lateral line, support cells presumably have the ability to replenish themselves. Utilizing novel transgenic lines, we identified support cell populations with distinct progenitor identities. These populations show differences in their ability to generate new hair cells during homeostasis and regeneration. Targeted ablation of support cells reduced the number of regenerated hair cells. Furthermore, progenitors regenerated after targeted support cell ablation in the absence of hair cell damage. We also determined that distinct support cell populations are independently regulated by Notch signaling. The existence of independent progenitor populations could provide flexibility for the continued generation of new hair cells under a variety of conditions throughout the life of the animal.

Highlights

The regenerative potential of a given tissue is dependent on the availability of progenitor cells that are able to functionally replace lost or damaged cells within that tissue
We show that Notch signaling differentially regulates these populations. These results demonstrate that there are a number of distinct progenitor populations within lateral line neuromasts that are independently regulated, providing flexibility for hair cell replacement under a variety of circumstances
We noticed that at the same timepoint that 28% of EdU-positive cells remained support cells (Figure 1E and B arrowheads). We hypothesized that these cells may represent hair cell progenitors that had been replaced via proliferation

Summary

Introduction

The regenerative potential of a given tissue is dependent on the availability of progenitor cells that are able to functionally replace lost or damaged cells within that tissue. Bulge cells in the hair follicle can repair the surrounding epidermis (Rompolas and Greco, 2014; Hsu et al, 2014), new intestinal epithelial cells arise from crypt cells (Santos et al, 2018; Yousefi et al, 2017), and horizontal and globose basal cells can regenerate cells in the olfactory epithelium (Choi and Goldstein, 2018; Schwob et al, 2017) Depletion of these progenitors can severely diminish the regenerative capacity of the tissue, and tissues that lack a progenitor pool altogether are unable to regenerate. The support cell proliferation that follows hair cell death occurs mainly in the dorsal and ventral compartments of the neuromast (Romero-Carvajal et al, 2015), indicating that progenitor identity

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