Insights into sensory hair cell regeneration from the zebrafish lateral line

AbstractLoss of sensory hair cells leads to deafness and balance deficiencies. In contrast to mammalian hair cells, zebrafish ear and lateral line hair cells regenerate from poorly characterized, proliferating support cells. Equally ill-defined is the gene regulatory network underlying the progression of support cells to cycling hair cell progenitors and differentiated hair cells. We used single cell RNA-Sequencing (scRNA-Seq) of lateral line sensory organs and uncovered five different support cell types, including quiescent and activated stem cells. In silico ordering of support cells along a developmental trajectory identified cells that self-renew and new groups of genes required for hair cell differentiation. scRNA-Seq analyses of fgf3 mutants, in which hair cell regeneration is increased, demonstrates that Fgf and Notch signaling inhibit proliferation of support cells in parallel by inhibiting Wnt signaling. Our scRNA-Seq analyses set the foundation for mechanistic studies of sensory organ regeneration and is crucial for identifying factors to trigger hair cell production in mammals. As a resource, we implemented a shiny application that allows the community to interrogate cell type specific expression of genes of interest.

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Faculty Opinions recommendation of Identification of modulators of hair cell regeneration in the zebrafish lateral line.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.714447804.790002804 ◽

2012 ◽

Author(s):

Andy Groves

Keyword(s):

Hair Cell ◽

Lateral Line ◽

Cell Regeneration ◽

Hair Cell Regeneration

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Tail of two fishies: age and afferents influence zebrafish lateral‐line hair cell regeneration

The Journal of Physiology ◽

10.1113/jp282012 ◽

2021 ◽

Author(s):

Lavinia Sheets

Keyword(s):

Hair Cell ◽

Lateral Line ◽

Cell Regeneration ◽

Hair Cell Regeneration

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Macrophages Respond Rapidly to Ototoxic Injury of Lateral Line Hair Cells but Are Not Required for Hair Cell Regeneration

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2020.613246 ◽

2021 ◽

Vol 14 ◽

Author(s):

Mark E. Warchol ◽

Angela Schrader ◽

Lavinia Sheets

Keyword(s):

Hair Cell ◽

Inner Ear ◽

Lateral Line ◽

Hair Cells ◽

Control Fish ◽

Cell Regeneration ◽

Cellular Interactions ◽

Hair Cell Regeneration ◽

Genetic Ablation ◽

Larval Zebrafish

The sensory organs of the inner ear contain resident populations of macrophages, which are recruited to sites of cellular injury. Such macrophages are known to phagocytose the debris of dying cells but the full role of macrophages in otic pathology is not understood. Lateral line neuromasts of zebrafish contain hair cells that are nearly identical to those in the inner ear, and the optical clarity of larval zebrafish permits direct imaging of cellular interactions. In this study, we used larval zebrafish to characterize the response of macrophages to ototoxic injury of lateral line hair cells. Macrophages migrated into neuromasts within 20 min of exposure to the ototoxic antibiotic neomycin. The number of macrophages in the near vicinity of injured neuromasts was similar to that observed near uninjured neuromasts, suggesting that this early inflammatory response was mediated by “local” macrophages. Upon entering injured neuromasts, macrophages actively phagocytosed hair cell debris. The injury-evoked migration of macrophages was significantly reduced by inhibition of Src-family kinases. Using chemical-genetic ablation of macrophages before the ototoxic injury, we also examined whether macrophages were essential for the initiation of hair cell regeneration. Results revealed only minor differences in hair cell recovery in macrophage-depleted vs. control fish, suggesting that macrophages are not essential for the regeneration of lateral line hair cells.

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Suppression of Inflammation Delays Hair Cell Regeneration and Functional Recovery Following Lateral Line Damage in Zebrafish Larvae

10.1101/2020.02.26.962753 ◽

2020 ◽

Cited By ~ 1

Author(s):

Ru Zhang ◽

Xiao-Peng Liu ◽

Ya-Juan Li ◽

Ming Wang ◽

Lin Chen ◽

...

Keyword(s):

Hair Cell ◽

Functional Recovery ◽

Lateral Line ◽

Hair Cells ◽

Calcium Imaging ◽

Inflammatory Responses ◽

Early Stage ◽

Cell Regeneration ◽

Hair Cell Regeneration ◽

Cochlear Hair Cells

AbstractBackgroundHuman cochlear hair cells cannot spontaneously regenerate after loss. In contrast, those in fish and amphibians have a remarkable ability to regenerate after damaged. Previous studies focus on signaling mechanisms of hair cell regeneration, such as Wnt and Notch signals but seldom on the fact that the beginning of regeneration is accompanied by a large number of inflammatory responses. The detailed role of this inflammation in hair cell regeneration is still unknown. In addition, there is no appropriate behavioral method to quantitatively evaluate the functional recovery of lateral line hair cells after regeneration.ResultsIn this study, we found that when inflammation was suppressed, the regeneration of lateral line hair cells and the recovery of the rheotaxis of the larvae were significantly delayed. Calcium imaging showed that the function of the neuromasts in the inflammation-inhibited group was weaker than that in the non-inflammation-inhibited group at the Early Stage of regeneration, and returned to normal at the Late Stage. Calcium imaging also revealed the cause of the mismatch between the function and quantity during regeneration.ConclusionsOur results, meanwhile, suggest that suppressing inflammation delays hair cell regeneration and functional recovery when hair cells are damaged. This study may provide a new knowledge for how to promote hair cell regeneration and functional recovery in adult mammals.

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