Radial glia in the zebrafish brain: Functional, structural, and physiological comparison with the mammalian glia

Abstract

The neuroscience community has witnessed a tremendous expansion of glia research. Glial cells are now on center stage with leading roles in the development, maturation, and physiology of brain circuits. Over the course of evolution, glia have highly diversified and include the radial glia, astroglia or astrocytes, microglia, oligodendrocytes, and ependymal cells, each having dedicated functions in the brain. The zebrafish, a small teleost fish, is no exception to this and recent evidences point to evolutionarily conserved roles for glia in the development and physiology of its nervous system. Due to its small size, transparency, and genetic amenability, the zebrafish has become an increasingly prominent animal model for brain research. It has enabled the study of neural circuits from individual cells to entire brains, with a precision unmatched in other vertebrate models. Moreover, its high neurogenic and regenerative potential has attracted a lot of attention from the research community focusing on neural stem cells and neurodegenerative diseases. Hence, studies using zebrafish have the potential to provide fundamental insights about brain development and function, and also elucidate neural and molecular mechanisms of neurological diseases. We will discuss here recent discoveries on the diverse roles of radial glia and astroglia in neurogenesis, in modulating neuronal activity and in regulating brain homeostasis at the brain barriers. By comparing insights made in various animal models, particularly mammals and zebrafish, our goal is to highlight the similarities and differences in glia biology among species, which could set new paradigms relevant to humans.

Functional properties of habenular neurons are determined by developmental stage and sequential neurogenesis

“…In this arrangement, youngest neurons are located closer to the neural progenitors of the habenula on the medial wall, while the oldest habenular neurons are located closer to the lateral wall. Similar sequential stacking of newly born neurons was also observed during forebrain development in both zebrafish (65,66) and rodents (6,67). Moreover, such a sequential order of neurogenesis contributes to different neural subtypes in the zebrafish hindbrain and spinal cord (8-10), as well as the rodent entorhinal cortex (5).…”

Common and Distinct Features of Adult Neurogenesis and Regeneration in the Telencephalon of Zebrafish and Mammals

“…An interesting evolutionary aspect to stress is that astrocytes derived from RGCs in mouse express markers like GFAP, vimentin, glutamin synthase and S100β, which are also expressed by zebrafish RGCs ( März et al, 2010 ; Kroehne et al, 2011 ; Dimou and Gotz, 2014 ; Wang et al, 2019 ). The fact that the brain, in particular the telencephalon, of zebrafish is devoid of astrocytes, raises the question of which cells adopted their astrocytic functions [i.e., in blood brain barrier (BBB) establishment, neurotransmitter uptake, ionic regulation, and neurosteroidogenesis] ( Jurisch-Yaksi et al, 2020 ). More and more data in fish point to the general idea that zebrafish RGCs fulfill the functions of astrocytes.…”

“…These data suggest the existence of heterogeneity between RGCs throughout the brain but also within the telencephalon ( Figure 2 ). In addition, a recent review documents the heterogeneity within the neural progenitor population in zebrafish with some progenitors expressing genes involved in astroglial functions and others expressing typical ependymal markers ( Jurisch-Yaksi et al, 2020 ). Also, among pallial RGCs, some seem to be deeply quiescent and others appear to constitute a self-renewing reservoir ( Than-Trong et al, 2020 ).…”

Cellular Mechanisms Participating in Brain Repair of Adult Zebrafish and Mammals After Injury

“…In zebrafish, the main neurogenic niches that have been studied during adulthood are located in the telencephalon, the optic tectum and the cerebellum. The telencephalon remains undoubtedly the most investigated region of the brain, because it shares many features and homologies with the mammalian telencephalon, particularly considering adult neurogenesis (Kizil et al, 2012a;Diotel et al, 2020;Jurisch-Yaksi et al, 2020;Than-Trong et al, 2020). In the telencephalon, several studies have explored the identity and the diversity of the neural/progenitor cells sustaining the strong neurogenic activity observed in the different telencephalic subdomains (Pellegrini et al, 2007;Zupanc, 2008;März et al, 2010;Kizil et al, 2012a;Lindsey et al, 2012;Schmidt et al, 2014).…”

“…However, RGCs are suggested to sustain many astrocytic features and functions, such as typical marker expression, steroidogenesis, blood-brain barrier establishment and neurogenic properties (Diotel et al, 2018;Jurisch-Yaksi et al, 2020). Although, no astrogliosis was observed in zebrafish after telencephalic injury, reactive RGC gliosis occurs, as shown by the up-regulation of GFAP and vimentin as well as the hypertrophy of RGC glial processes (Kroehne et al, 2011).…”