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

2020 ◽  
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.

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

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1451
Author(s):  
Ru Zhang ◽  
Xiaopeng Liu ◽  
Yajuan Li ◽  
Ming Wang ◽  
Lin Chen ◽  
...  
Keyword(s):  
Hair Cell ◽  
Functional Recovery ◽  
Lateral Line ◽  
Hair Cells ◽  
Calcium Imaging ◽  
Inflammatory Factors ◽  
Cell Regeneration ◽  
Human Beings ◽  
Hair Cell Regeneration ◽  
Zebrafish Larvae

Cochlear hair cells in human beings cannot regenerate after loss; however, those in fish and other lower species can. Recently, the role of inflammation in hair cell regeneration has been attracting the attention of scientists. In the present study, we investigated how suppression of inflammatory factors affects hair cell regeneration and the functional recovery of regenerated hair cells in zebrafish. We killed hair cells in the lateral line of zebrafish larvae with CuSO4 to induce an inflammatory response and coapplied BRS-28, an anti-inflammatory agent to suppress the inflammation. The recovery of the hair cell number and rheotaxis was slower when CuSO4 and BRS-28 were coapplied than when CuSO4 was applied alone. The recovery of hair cell count lagged behind that of the calcium imaging signal during the regeneration. The calcium imaging signal in the neuromasts in the inflammation-inhibited group was weaker than that in the noninflammation-inhibited group at the early stage of regeneration, although it returned to normal at the late stage. Our study demonstrates that suppressing inflammation by BRS-28 delays hair cell regeneration and functional recovery when hair cells are damaged. We suspect that BRS-28 inhibits pro-inflammatory factors and thereby reduces the migration of macrophages to delay the regeneration of hair cells.

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

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.

scholarly journals Macrophages respond rapidly to ototoxic injury of lateral line hair cells but are not required for hair cell regeneration

2020 ◽  
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

AbstractThe 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 similar 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 close proximity 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. Such phagocytosis was significantly reduced by inhibiting Src-family kinases. Using chemical-genetic ablation of macrophages prior to ototoxic injury, we also examined whether macrophages were essential for the initiation of hair cell regeneration after neomycin exposure. 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.

scholarly journals scRNA-Seq reveals distinct stem cell populations that drive hair cell regeneration after loss of Fgf and Notch signaling

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Mark E Lush ◽  
Daniel C Diaz ◽  
Nina Koenecke ◽  
Sungmin Baek ◽  
Helena Boldt ◽  
...  
Keyword(s):  
Hair Cell ◽  
Notch Signaling ◽  
Lateral Line ◽  
Hair Cells ◽  
Cell Types ◽  
Developmental Trajectory ◽  
Cell Regeneration ◽  
Hair Cell Regeneration ◽  
Organ Regeneration ◽  
Hair Cell Differentiation

Loss 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 support cells. Equally ill-defined is the gene regulatory network underlying the progression of support cells to differentiated hair cells. scRNA-Seq of lateral line organs uncovered five different support cell types, including quiescent and activated stem cells. Ordering of support cells along a developmental trajectory identified self-renewing cells and 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. The data is searchable and publicly accessible via a web-based interface.

scholarly journals Single cell RNA-Seq reveals distinct stem cell populations that drive sensory hair cell regeneration in response to loss of Fgf and Notch signaling

2018 ◽  
Author(s):  
Mark E. Lush ◽  
Daniel C. Diaz ◽  
Nina Koenecke ◽  
Sungmin Baek ◽  
Helena Boldt ◽  
...  
Keyword(s):  
Hair Cell ◽  
Notch Signaling ◽  
Single Cell ◽  
Lateral Line ◽  
Hair Cells ◽  
Developmental Trajectory ◽  
Cell Regeneration ◽  
Hair Cell Regeneration ◽  
Specific Expression ◽  
Sensory Hair

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.

Delta1 expression during avian hair cell regeneration

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 961-973 ◽  
Author(s):  
J.S. Stone ◽  
E.W. Rubel
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Cell Injury ◽  
Basilar Papilla ◽  
Cell Regeneration ◽  
Mrna Levels ◽  
Hair Cell Regeneration ◽  
Drug Induced ◽  
In Cells

Postembryonic production of hair cells, the highly specialized receptors for hearing, balance and motion detection, occurs in a precisely controlled manner in select species, including avians. Notch1, Delta1 and Serrate1 mediate cell specification in several tissues and species. We examined expression of the chicken homologs of these genes in the normal and drug-damaged chick inner ear to determine if signaling through this pathway changes during hair cell regeneration. In untreated post-hatch chicks, Delta1 mRNA is abundant in a subpopulation of cells in the utricle, which undergoes continual postembryonic hair cell production, but it is absent from all cells in the basilar papilla, which is mitotically quiescent. By 3 days after drug-induced hair cell injury, Delta1 expression is highly upregulated in areas of cell proliferation in both the utricle and basilar papilla. Delta1 mRNA levels are elevated in progenitor cells during DNA synthesis and/or gap 2 phases of the cell cycle and expression is maintained in both daughter cells immediately after mitosis. Delta1 expression remains upregulated in cells that differentiate into hair cells and is downregulated in cells that do not acquire the hair cell fate. Delta1 mRNA levels return to normal by 10 days after hair cell injury. Serrate1 is expressed in both hair cells and support cells in the utricle and basilar papilla, and its expression does not change during the course of drug-induced hair cell regeneration. In contrast, Notch1 expression, which is limited to support cells in the quiescent epithelium, is increased in post-M-phase cell pairs during hair cell regeneration. This study provides initial evidence that Delta-Notch signaling may be involved in maintaining the correct cell types and patterns during postembryonic replacement of sensory epithelial cells in the chick inner ear.

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