Abstract
Microglia are the resident macrophages of the brain. Over the past decade, our understanding of the function of these cells has significantly improved. Microglia do not only play important roles in the healthy brain but are involved in almost every brain pathology. Gene expression profiling allowed to distinguish microglia from other macrophages and revealed that the full microglia signature can only be observed in vivo. Thus, animal models are irreplaceable to understand the function of these cells. One of the popular models to study microglia is the zebrafish larva. Due to their optical transparency and genetic accessibility, zebrafish larvae have been employed to understand a variety of microglia functions in the living brain. Here, we performed RNA sequencing of larval zebrafish microglia at different developmental time points: 3, 5, and 7 days post fertilization (dpf). Our analysis reveals that larval zebrafish microglia rapidly acquire the core microglia signature and many typical microglia genes are expressed from 3 dpf onwards. The majority of changes in gene expression happened between 3 and 5 dpf, suggesting that differentiation mainly takes place during these days. Furthermore, we compared the larval microglia transcriptome to published data sets of adult zebrafish microglia, mouse microglia, and human microglia. Larval microglia shared a significant number of expressed genes with their adult counterparts in zebrafish as well as with mouse and human microglia. In conclusion, our results show that larval zebrafish microglia mature rapidly and express the core microglia gene signature that seems to be conserved across species.
Highlights
Microglia represent the tissue-resident macrophage population of the brain
After the global analysis of gene expression changes, we focused on genes that are involved in processes required for invasion of macrophages into the brain, differentiation into microglia, and microglial functions (Table S2)
We compared the genes that we have identified to be differentially expressed in zebrafish microglia at 3, 5, and 7 dpf to the 1,297 differentially expressed genes found in human microglia (Galatro et al, 2017)
Summary
Microglia represent the tissue-resident macrophage population of the brain. Microglia are derived from primitive macrophages that colonize the central nervous system (CNS) early during development where. Have provided an in-depth understanding of the microglia gene expression signature This allows a clear discrimination of microglia from other brain cells, and other populations of macrophages (Butovsky et al, 2013). The mechanisms underlying these functions are the same as those employed by mammalian microglia, suggesting a high degree of conservation across species (Sieger & Peri, 2013) In zebrafish, these larval microglia seem to be replaced by a second wave of definitive microglia that persist throughout adulthood and are derived from cmyb-dependent hematopoietic stem cells (Ferrero et al, 2018; Xu et al, 2015). Our new gene expression data combined with previous functional studies on larval microglia, underscore the suitability of the larval zebrafish to study microglial functions and mechanisms
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
