Analysis of Apoptotic Cell Clearance by Microglia in Zebrafish Mutants Lacking Havcr1, a Putative Phosphatidylserine Receptor
Additional Funding Sources
The project described was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant No. P20GM103408. This project is supported by a 2019-2020 STEM Undergraduate Research Grant from the Higher Education Research Council.
Presentation Date
7-2020
Abstract
The retina is made functional by complex interactions of various cell types unique to the central nervous system. While neurons and glia are well appreciated in this context, the microglia, a lesser understood cell type, has emerged as an important player. Microglia are resident phagocytes that colonize the central nervous system (brain and retina) early in vertebrate development. Recent work indicates that microglia have a variety of functions in development and homeostasis, but the genes and pathways that are involved, and therefore molecular mechanisms, are poorly understood. A well-described function of microglia is the phagocytic clearance of apoptotic cells during normal development as well as in contexts of tissue damage or degeneration. However, the genes required for this function remain to be fully elucidated. Recent transcriptome analysis published by our lab has shown zebrafish microglia express high levels of the gene havcr1. Sequence and genomic comparisons indicate havcr1 is a receptor for Phosphatidylserine (PS), which is exposed on the surface of dying cells. Therefore, we hypothesize that havcr1 has a function in the recognition and clearance of apoptotic cells by microglia. We propose to use the zebrafish to reveal the function of havcr1 in the vertebrate retina, by the following objectives: (1) Demonstrate that microglia express havcr1 using in situ hybridization, and (2) Determine if clearance of apoptotic cells during development is reduced in havcr1 mutants. This work will increase mechanistic understanding of apoptotic cell clearance by microglia and will provide a novel genetic tool for future experiments.
Analysis of Apoptotic Cell Clearance by Microglia in Zebrafish Mutants Lacking Havcr1, a Putative Phosphatidylserine Receptor
The retina is made functional by complex interactions of various cell types unique to the central nervous system. While neurons and glia are well appreciated in this context, the microglia, a lesser understood cell type, has emerged as an important player. Microglia are resident phagocytes that colonize the central nervous system (brain and retina) early in vertebrate development. Recent work indicates that microglia have a variety of functions in development and homeostasis, but the genes and pathways that are involved, and therefore molecular mechanisms, are poorly understood. A well-described function of microglia is the phagocytic clearance of apoptotic cells during normal development as well as in contexts of tissue damage or degeneration. However, the genes required for this function remain to be fully elucidated. Recent transcriptome analysis published by our lab has shown zebrafish microglia express high levels of the gene havcr1. Sequence and genomic comparisons indicate havcr1 is a receptor for Phosphatidylserine (PS), which is exposed on the surface of dying cells. Therefore, we hypothesize that havcr1 has a function in the recognition and clearance of apoptotic cells by microglia. We propose to use the zebrafish to reveal the function of havcr1 in the vertebrate retina, by the following objectives: (1) Demonstrate that microglia express havcr1 using in situ hybridization, and (2) Determine if clearance of apoptotic cells during development is reduced in havcr1 mutants. This work will increase mechanistic understanding of apoptotic cell clearance by microglia and will provide a novel genetic tool for future experiments.