[
Genetics,
2023]
The nematode Caenorhabditis elegans is a research model organism particularly suited to the mechanistic understanding of synapse genesis in the nervous system. Armed with powerful genetics, knowledge of complete connectomics, and modern genomics, studies using C. elegans have unveiled multiple key regulators in the formation of a functional synapse. Importantly, many signaling networks display remarkable conservation throughout animals, underscoring the contributions of C. elegans research to advance the understanding of our brain. In this chapter, we will review up-to-date information of the contribution of C. elegans to the understanding of chemical synapses, from structure to molecules and to synaptic remodeling.
[
WormBook,
2008]
The role of neuropeptides in modulating behavior is slowly being elucidated. With the sequencing of the C. elegans genome, the extent of the neuropeptide genes in C. elegans can be determined. To date, 113 neuropeptide genes encoding over 250 distinct neuropeptides have been identified. Of these, 40 genes encode insulin-like peptides, 31 genes encode FMRFamide-related peptides, and 42 genes encode non-insulin, non-FMRFamide-related neuropeptides. As in other systems, C. elegans neuropeptides are derived from precursor molecules that must be post-translationally processed to yield the active peptides. These precursor molecules contain a single peptide, multiple copies of a single peptide, multiple distinct peptides, or any combination thereof. The neuropeptide genes are expressed extensively throughout the nervous system, including in sensory, motor, and interneurons. In addition, some of the genes are also expressed in non-neuronal tissues, such as the somatic gonad, intestine, and vulval hypodermis. To address the effects of neuropeptides on C. elegans behavior, animals in which the different neuropeptide genes are inactivated or overexpressed are being isolated. In a complementary approach the receptors to which the neuropeptides bind are also being identified and examined. Among the knockout animals analyzed thus far, defects in locomotion, dauer formation, egg laying, ethanol response, and social behavior have been reported. These data suggest that neuropeptides have a modulatory role in many, if not all, behaviors in C. elegans.
[
WormBook,
2006]
Most rapid excitatory synaptic signaling is mediated by glutamatergic neurotransmission. An important challenge in neurobiology is to understand the molecular architecture of functional glutamatergic synapses. By combining the techniques of genetics, molecular biology and electrophysiology in C. elegans we have the potential to identify and characterize the molecules that contribute to the function of glutamatergic synapses. In C. elegans both excitatory and inhibitory ionotropic glutamate receptors are linked to neural circuits and behavior. Genetic analysis has identified genes required for receptor expression, trafficking, localization, stabilization and function at synapses. Significantly, novel proteins required for glutamate receptor function have been discovered in the worm. These advances may also lead to a better understanding of glutamatergic signaling in vertebrates.
[
WormBook,
2006]
Small GTPases of the Ras superfamily are key regulators of diverse cellular and developmental events, including differentiation, cell division, vesicle transport, nuclear assembly, and control of the cytoskeleton. The C. elegans genome encodes 56 members of the major Ras GTPase subfamilies, including the Ras/Ral/Rap family, the Rho family, the Rab family, Ran, and the Arf/Sar family. Studies in C. elegans have shown that Ras/Rap family members control cell fate specification and differentiation; Rho GTPases control morphogenesis and actin dynamics, including axon pathfinding and cell migration; Rab GTPases control synaptic vesicle trafficking and release and gene expression responses in innate immunity; the Ran GTPase controls nuclear import/export, nuclear reassembly after mitosis, and kinetechore association with microtubules; and Arf/Sar GTPases control morphogenesis and microtubule organization and possibly cilia development. Functions for many of the small GTPases remain to be discovered, and continuing studies in C. elegans will elucidate the roles of these molecules in animal development.