From Neural Tube Formation Through the Differentiation of Spinal Cord Neurons: Ion Channels in Action During Neural Development

Abstract

Ion channels are expressed throughout nervous system development. The type and diversity of conductances and gating mechanisms vary at different developmental stages and with the progressive maturational status of neural cells. The variety of ion channels allows for distinct signaling mechanisms in developing neural cells that in turn regulate the needed cellular processes taking place during each developmental period. These include neural cell proliferation and neuronal differentiation, which are crucial for developmental events ranging from the earliest steps of morphogenesis of the neural tube through the establishment of neuronal circuits. Here, we compile studies assessing the ontogeny of ionic currents in the developing nervous system. We then review work demonstrating a role for ion channels in neural tube formation, to underscore the necessity of the signaling downstream ion channels even at the earliest stages of neural development. We discuss the function of ion channels in neural cell proliferation and neuronal differentiation and conclude with how the regulation of all these morphogenetic and cellular processes by electrical activity enables the appropriate development of the nervous system and the establishment of functional circuits adapted to respond to a changing environment.

The Efficiency of Direct Maturation: the Comparison of Two hiPSC Differentiation Approaches into Motor Neurons

“…To further characterize the neurons derived from 28 days differentiation via approaches A and B, the expression of various genes characteristic of motor neurogenesis [19], neuronal ion channels [20], neurotrophins [21], and neurotransmitters [22] was determined. As shown in Figure 3, genes were significantly differentially expressed in cells of both approaches A and B compared to NPC (fold regulation ≥ 2:0 and ≤ -2.0 in combination with p < 0:05).…”

Maternally derived hormones, neurosteroids and the development of behaviour

“…Already, in very early stages of embryonic development, electrical activity is produced by neurons and GABA A receptors are expressed in neurons across tissues [63][64][65][66][67][68]. In these early stage embryos, spontaneous neural activity, which is not triggered by environmental stimuli, is essential for key developmental processes including neural tube formation, neurogenesis, cell migration, programmed cell death, cellular differentiation and the formation of local and long-range neural connections [66,[68][69][70][71]. Electrical activity in developing neurons can also influence cell growth and neurite branching as well as modulate responses to chemical guidance cues, which may have major implications for the degree and strength of connectivity in neural circuits important for behaviour (figure 1c,d) [66].…”

“…The activity of neurotransmitter-mediated ion channels, such as from GABA A receptors, are essential for normal functioning and development of the central nervous system even during the very earliest stages of life (e.g. neural tube formation, neurogenesis and neural cell migration [70]). In contrast with the mutant mouse example above [104], mutations dramatically altering expression patterns of these receptors are more likely to disrupt key GABA-binding related functions and result in catastrophic consequences very early in development (e.g.…”

Electro‐Stimulation, a Promising Therapeutic Treatment Modality for Tissue Repair: Emerging Roles of Sulfated Glycosaminoglycans as Electro‐Regulatory Mediators of Intrinsic Repair Processes

“…[ 42,44 ] The neuron is a well‐known electrosensitive cell type which develops into extensive communication networks throughout the body that direct the activity of other cell types in multisystem components. [ 45 ] Ion channels facilitate the development of the nervous system and are controlled by various gating mechanisms during developmental stages and the maturation of neural and related cell types. Variation in ion channels provides distinct signaling mechanisms in neural cell development supporting neural cell proliferation and neuronal differentiation, critical to developmental events which drive the earliest stages of the morphogenesis of the neural tube through to the establishment of diverse neuronal systems throughout the embryo and formation of the spinal cord, brain stem, and brain.…”

“…Variation in ion channels provides distinct signaling mechanisms in neural cell development supporting neural cell proliferation and neuronal differentiation, critical to developmental events which drive the earliest stages of the morphogenesis of the neural tube through to the establishment of diverse neuronal systems throughout the embryo and formation of the spinal cord, brain stem, and brain. [ 45 ] Something that also needs to be considered in these developmental tissue processes is the role of proteoglycan GAG side chains which carry counterions and their potential roles as ion reservoirs in specific developmental niches. [ 46,47 ] KS is a widely distributed GAG in sensory tissues and displays variable sulfation levels which may facilitate fine levels of control over the counterions they make available for the generation of ion channel generated events in specific developmental contexts.…”