Dataset Information

Bioinformatic analysis and functional predictions of selected regeneration-associated transcripts expressed by zebrafish microglia.

ABSTRACT: Background: Unlike mammals, zebrafish have a remarkable capacity to regenerate a variety of tissues, including central nervous system tissue. The function of macrophages in tissue regeneration is of great interest, as macrophages respond and participate in the landscape of events that occur following tissue injury in all vertebrate species examined. Understanding macrophage populations in regenerating tissue (such as in zebrafish) may inform strategies that aim to regenerate tissue in humans. We recently published an RNA-seq experiment that identified genes enriched in microglia/macrophages in regenerating zebrafish retinas. Interestingly, a small number of transcripts differentially expressed by retinal microglia/macrophages during retinal regeneration did not have predicted orthologs in human or mouse. We reasoned that at least some of these genes could be functionally important for tissue regeneration, but most of these genes have not been studied experimentally and their functions are largely unknown. To reveal their possible functions, we performed a variety of bioinformatic analyses aimed at identifying the presence of functional protein domains as well as orthologous relationships to other species.

Results: Our analyses identified putative functional domains in predicted proteins for a number of selected genes. For example, we confidently predict kinase function for one gene, cytokine/chemokine function for another, and carbohydrate enzymatic function for a third. Predicted orthologs were identified for some, but not all, genes in species with described regenerative capacity, and functional domains were consistent with identified orthologs. Comparison to other published gene expression datasets suggest that at least some of these genes could be important in regenerative responses in zebrafish and not necessarily in response to microbial infection.

Conclusions: This work reveals previously undescribed putative function of several genes implicated in regulating tissue regeneration. This will inform future work to experimentally determine the function of these genes in vivo, and how these genes may be involved in microglia/macrophage roles in tissue regeneration.

SUBMITTER: Issaka Salia O

PROVIDER: S-EPMC7720500 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Bioinformatic analysis and functional predictions of selected regeneration-associated transcripts expressed by zebrafish microglia.

Issaka Salia Ousseini O Mitchell Diana M DM

BMC genomics 20201207 1

<h4>Background</h4>Unlike mammals, zebrafish have a remarkable capacity to regenerate a variety of tissues, including central nervous system tissue. The function of macrophages in tissue regeneration is of great interest, as macrophages respond and participate in the landscape of events that occur following tissue injury in all vertebrate species examined. Understanding macrophage populations in regenerating tissue (such as in zebrafish) may inform strategies that aim to regenerate tissue in hum ...[more]

PMID: 33287696

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Project description:Key pointsWe investigated hair-cell regeneration in the zebrafish lateral line following the application of the ototoxic compound copper. In early-larval zebrafish (<10 days post-fertilisation), regenerated hair cells drive action potentials (APs) in the afferent neurons 24 h post-copper treatment (24 hpt). Full regeneration of the early-larval neuromasts, the organs containing the hair cells, requires ∼48 h due to the progressive addition of hair cells and synaptic refinement. In older larval zebrafish, regenerated hair cells are active and drive afferent APs by 48 hpt, which is comparable to larvae, but the functional recovery of their neuromasts requires >120 hpt. Afferent terminals within the regenerating neuromast appear to initially contact supporting cells, and their complete ablation prevents the timely reappearance of supporting cells and hair cells. We conclude that the regeneration of zebrafish neuromasts is slower after the initial developmental stages, and that the afferent input plays a key role in driving this process.AbstractHair cells are mechanosensory receptors responsible for transducing auditory and vestibular information into electrical signals, which are then transmitted with remarkable precision to afferent neurons. Different from mammals, the hair cells of lower vertebrates, including those present in the neuromasts of the zebrafish lateral line, regenerate following environmental or chemical insults. Here we investigate the time course of regeneration of hair cells in vivo using electrophysiology, two-photon imaging and immunostaining applied to wild-type and genetically encoded fluorescent indicator zebrafish lines. Functional hair cells drive spontaneous action potentials in the posterior lateral line afferent fibres, the frequency of which progressively increases over the first 10 days post-fertilisation (dpf). Higher firing-rate fibres are only observed from ∼6 dpf. Following copper treatment, newly formed hair cells become functional and are able to drive APs in the afferent fibres within 48 h in both early-larval (≤8 dpf) and late-larval (12-17 dpf) zebrafish. However, the complete functional regeneration of the entire neuromast is delayed in late-larval compared to early-larval zebrafish. We propose that while individual regenerating hair cells can rapidly become active, the acquisition of fully functional neuromasts progresses faster at early-larval stages, a time when hair cells are still under development. At both ages, the afferent terminals in the regenerating neuromast appear to make initial contact with supporting cells. The ablation of the lateral line afferent neurons prevents the timely regeneration of supporting cells and hair cells. These findings indicate that the afferent system is likely to facilitate or promote the neuromast regeneration process.

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Dataset Information

Bioinformatic analysis and functional predictions of selected regeneration-associated transcripts expressed by zebrafish microglia.

Publications

Bioinformatic analysis and functional predictions of selected regeneration-associated transcripts expressed by zebrafish microglia.

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