More Than Mortar: Glia as Architects of Nervous System Development and Disease

Abstract

Glial cells are an essential component of the nervous system of vertebrates and invertebrates. In the human brain, glia are as numerous as neurons, yet the importance of glia to nearly every aspect of nervous system development has only been expounded over the last several decades. Glia are now known to regulate neural specification, synaptogenesis, synapse function, and even broad circuit function. Given their ubiquity, it is not surprising that the contribution of glia to neuronal disease pathogenesis is a growing area of research. In this review, we will summarize the accumulated evidence of glial participation in several distinct phases of nervous system development and organization—neural specification, circuit wiring, and circuit function. Finally, we will highlight how these early developmental roles of glia contribute to nervous system dysfunction in neurodevelopmental and neurodegenerative disorders.

Growing Glia: Cultivating Human Stem Cell Models of Gliogenesis in Health and Disease

“…Throughout evolutionary time, increased complexity of the nervous system has been accompanied by more numerous and diverse glial populations ( Lago-Baldaia et al, 2020 ). Evolutionary comparisons of human and rodent glia have repeatedly uncovered uniquely hominid features at molecular ( Lui et al, 2014 ; Berto et al, 2019 ), functional ( Zhang Y. et al, 2016 ), and morphological levels ( Oberheim et al, 2012 ).…”

The Contribution of Microglia to the Development and Maturation of the Visual System

“…Apoptosis involves the induction of a signaling cascade that ultimately leads to break down of a cell's proteome by activated caspases (Elmore, 2007). Induction of this process depends on the balance between pro-death and pro-survival signals, which can be regulated by glia (Lago-Baldaia et al, 2020). Microglia in particular may mediate induction of apoptosis in a number of ways depending on the developmental context.…”

Critical Involvement of Glial Cells in Manganese Neurotoxicity

“…The days when glial cells were considered the “glue” of synapses are fortunately long past gone. Nowadays, increasing evidence has emphasized their crucial role in proper brain functioning and CNS development [ 18 ]. Indeed, these cells provide structural, trophic, and metabolic support to neurons [ 19 ] and play an active role in important brain functions such as the uptake and synthesis of neurotransmitters, buffering of ion strength, immunomodulation, and adult neurogenesis, acting as a part of the blood-brain barrier controlling the in and out of substances from the bloodstream to the brain, intercellular communication through the formation of a glial syncytium, regulation of synaptogenesis, and synaptic plasticity while associated to synapses [ 4 , 20 ].…”

“…A single human astrocyte is capable of ensheathing more than 100,000 synapses [ 5 ]. The best-characterized functions of these cells are the turnover of neurotransmitters, ion homeostasis, as a constituent of the neurovascular unit, synaptogenesis, neuronal remodeling, and so on [ 18 ]. Astrocytes can be classified at least into two main categories regarding their localization and morphology: fibrous in the white matter with a clear star shape, and protoplasmic in the grey matter with a more plain appearance [ 27 ].…”

“…Widely known as the resident immune cell of the CNS, microglia makes up about 10% of the CNS glia [ 22 ]. The leading roles of microglia are immune surveillance, extracellular matrix remodeling, clearance of cellular debris and synaptic pruning, neurogenesis regulation, among other functions [ 18 , 22 ]. Under basal conditions, microglia have a distinct ramified morphology with extended processes for CNS surveillance.…”