Insights Into Central Nervous System Glial Cell Formation and Function From Zebrafish

Abstract

The term glia describes a heterogenous collection of distinct cell types that make up a large proportion of our nervous system. Although once considered the glue of the nervous system, the study of glial cells has evolved significantly in recent years, with a large body of literature now highlighting their complex and diverse roles in development and throughout life. This progress is due, in part, to advances in animal models in which the molecular and cellular mechanisms of glial cell development and function as well as neuron-glial cell interactions can be directly studied in vivo in real time, in intact neural circuits. In this review we highlight the instrumental role that zebrafish have played as a vertebrate model system for the study of glial cells, and discuss how the experimental advantages of the zebrafish lend themselves to investigate glial cell interactions and diversity. We focus in particular on recent studies that have provided insight into the formation and function of the major glial cell types in the central nervous system in zebrafish.

Dominant-acting CSF1R variants cause microglial depletion and altered astrocytic phenotype in zebrafish and adult-onset leukodystrophy

“…Zebrafish as a neurobiology model allows exploring cells in embryonic development, in their natural environment by non-invasive in vivo examination. This has led to new fundamental insight in glial biology [ 11 , 71 , 78 ]. In addition, options for genetic targeting have improved, including editing of specific genetic variants identified in human disease as we show here.…”

Epigenetics and Neuroinflammation Associated With Neurodevelopmental Disorders: A Microglial Perspective

“…In mice, primitive microglia derived from yolk sac progenitors (erythromyeloid precursors) migrate into the brain around embryonic day (E) 9.5, where they differentiate into microglia, colonize various brain regions, and regulate neurodevelopment ( Prinz et al, 2019 ; Stratoulias et al, 2019 ; Thion and Garel, 2020 ; Sharma et al, 2021 ). The entry of primitive macrophages and colonization of the brain are also conserved in zebrafish, an alternative animal model for various diseases, including NDDs ( Xu et al, 2015 ; Réu et al, 2017 ; Ferrero et al, 2018 ; Bian et al, 2020 ; Neely and Lyons, 2021 ). When the second wave of hematopoiesis occurs in mice, microglia progenitors expressing homeobox B8 are generated in the yolk sac, are present in the aorta-gonad-mesonephros (AGM) and fetal liver, and seed into the brain around E12.5 ( De et al, 2018 ).…”

“…In mice, microglia derived from both primitive and definitive hematopoiesis coexist in the adult brain ( Sharma et al, 2021 ). Despite these differences, the core microglial gene expression signature and microglial functions, such as immune surveillance, cellular debris cleaning, response to injury, and integration with neural circuits, are conserved between mammals and zebrafish ( Mazzolini et al, 2020 ; Neely and Lyons, 2021 ).…”

Progress in leukodystrophies with zebrafish

“…From 18 hours post‐fertilization, zebrafish embryos start producing radial glia cells which give rise to neuronal and glial progenitors. In the ventral spinal cord, oligodendrocyte progenitor cells (OPCs) initially derive from precursors of motor neurons and start proliferating and differentiating into myelinating oligodendrocytes under the control of transcription factors such as olig2 or nkx2.2 (Kucenas et al, 2008; Neely & Lyons, 2021). Zebrafish oligodendrocytes can myelinate several axons, and time‐lapse experiments in zebrafish unveiled the conserved mechanism of myelin wrapping in vertebrates, with transient cytoplasmic channels enabling membrane trafficking and myelin growth (Snaidero et al, 2014).…”