Large-scale death of retinal astrocytes during normal development is non-apoptotic and implemented by microglia
| Autor: | Monica A. Lee, Robin M. Perelli, Jeremy N. Kay, Benjamin E. Reese, Emily G. O’Koren, Federica S. Brecha, Caroline R. Ackley, Caitlin E. Paisley, Daniel R. Saban, Jingjing Wang, Vanessa M. Puñal |
|---|---|
| Přispěvatelé: | Scheiffele, Peter |
| Rok vydání: | 2019 |
| Předmět: |
Nervous system
Pulmonology Apoptosis Cell Count Cell Communication Toxicology Pathology and Laboratory Medicine Transgenic Mice 0302 clinical medicine Genes Reporter Animal Cells Toxins Diphtheria Toxin Biology (General) Neurons Phagocytes Microglia Retinal Hemorrhage Diphtheria SOX9 Transcription Factor Cellular Types General Agricultural and Biological Sciences Cell signaling QH301-705.5 Ocular Anatomy Immune Cells 1.1 Normal biological development and functioning Toxic Agents Immunology Glial Cells General Biochemistry Genetics and Molecular Biology Retina 03 medical and health sciences Bacterial Proteins Upper Respiratory Tract Infections Reporter Eye Disease and Disorders of Vision Blood Cells PAX2 Transcription Factor Biology and Life Sciences Mice Inbred C57BL Luminescent Proteins 030104 developmental biology chemistry Genes Astrocytes Blood Vessels Neuroscience 030217 neurology & neurosurgery Developmental Biology Retinal Ganglion Cells Bacterial Diseases 0301 basic medicine Vascular Endothelial Growth Factor A Macroglial Cells Receptor Platelet-Derived Growth Factor alpha Inbred C57BL Medical and Health Sciences White Blood Cells chemistry.chemical_compound Medicine and Health Sciences Developmental Cell Death General Neuroscience Gene Expression Regulation Developmental Biological Sciences Infectious Diseases medicine.anatomical_structure Cell Processes Anatomy Research Article Astrocyte Receptor Signal Transduction Programmed cell death Ganglion Cells Mice Transgenic Biology Ocular System Underpinning research Glial Fibrillary Acidic Protein medicine Animals Microglial Cells General Immunology and Microbiology Agricultural and Veterinary Sciences Platelet-Derived Growth Factor alpha Neurosciences Afferent Neurons Retinal Cell Biology Newborn Animals Newborn Gene Expression Regulation Cellular Neuroscience Respiratory Infections |
| Zdroj: | PLoS biology, vol 17, iss 10 PLoS Biology PLoS Biology, Vol 17, Iss 10, p e3000492 (2019) |
| Popis: | Naturally occurring cell death is a fundamental developmental mechanism for regulating cell numbers and sculpting developing organs. This is particularly true in the nervous system, where large numbers of neurons and oligodendrocytes are eliminated via apoptosis during normal development. Given the profound impact of death upon these two major cell populations, it is surprising that developmental death of another major cell type—the astrocyte—has rarely been studied. It is presently unclear whether astrocytes are subject to significant developmental death, and if so, how it occurs. Here, we address these questions using mouse retinal astrocytes as our model system. We show that the total number of retinal astrocytes declines by over 3-fold during a death period spanning postnatal days 5–14. Surprisingly, these astrocytes do not die by apoptosis, the canonical mechanism underlying the vast majority of developmental cell death. Instead, we find that microglia engulf astrocytes during the death period to promote their developmental removal. Genetic ablation of microglia inhibits astrocyte death, leading to a larger astrocyte population size at the end of the death period. However, astrocyte death is not completely blocked in the absence of microglia, apparently due to the ability of astrocytes to engulf each other. Nevertheless, mice lacking microglia showed significant anatomical changes to the retinal astrocyte network, with functional consequences for the astrocyte-associated vasculature leading to retinal hemorrhage. These results establish a novel modality for naturally occurring cell death and demonstrate its importance for the formation and integrity of the retinal gliovascular network. A study of the neonatal mouse retina shows that developmental cell death of retinal astrocytes does not occur by apoptosis but is instead mediated by microglia, which kill and engulf astrocytes to effect their developmental removal. |
| Databáze: | OpenAIRE |
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