[
Methods Mol Biol,
2006]
One benefit of the nematode Caenorhabditis elegans as a model system is the ease to conduct forward genetic screens and to isolate mutants with phenotypes of interest. However, identifying the mutated genes requires positional cloning, which can be laborious and time consuming. Insertional mutagenesis with a heterologous transposon bypasses the mapping steps and expedites the process of identifying the mutated genes. The Drosophila transposon Mos1 can be mobilized in the C. elegans germline to cause mutations. Mutagenic insertions are subsequently localized within the genome using inverse polymerase chain reaction. The mutagenicity of this technique is roughly one order of magnitude lower than chemical mutagens. However, the molecular identification of the mutated genes is extremely rapid. Therefore, before using Mos1-mediated mutagenesis, one must evaluate the trade-off between time spent screening for mutants vs time spent mapping and rescuing a mutation.
[
Med Sci (Paris),
2003]
The human brain contains 100 billion neurons and probably one thousand times more synapses. Such a system can be analyzed at different complexity levels, from cognitive functions to molecular structure of ion channels. However, it remains extremely difficult to establish links between these different levels. An alternative strategy relies on the use of much simpler animals that can be easily manipulated. In 1974, S. Brenner introduced the nematode Coenorhabditis elegans as a model system. This worm has a simple nervous system that only contains 302 neurons and about 7,000 synapses. Forward genetic screens are powerful tools to identify genes required for specific neuron functions and behaviors. Moreover, studies of mutant phenotypes can identify the function of a protein in the nervous system. The data that hove been obtained in C. elegans demonstrate a fascinating conservation of the molecular and cellular biology of the neuron between worms and mammals through more than 550 million years of evolution.
[
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.
[
Front Neurosci,
2022]
The appearance of synapses was a crucial step in the creation of the variety of nervous systems that are found in the animal kingdom. With increased complexity of the organisms came a greater number of synaptic proteins. In this review we describe synaptic proteins that contain the structural domains CUB, CCP, or TSP-1. These domains are found in invertebrates and vertebrates, and CUB and CCP domains were initially described in proteins belonging to the complement system of innate immunity. Interestingly, they are found in synapses of the nematode <i>C. elegans</i>, which does not have a complement system, suggesting an ancient function. Comparison of the roles of CUB-, CCP-, and TSP-1 containing synaptic proteins in various species shows that in more complex nervous systems, these structural domains are combined with other domains and that there is partial conservation of their function. These three domains are thus basic building blocks of the synaptic architecture. Further studies of structural domains characteristic of synaptic proteins in invertebrates such as <i>C. elegans</i> and comparison of their role in mammals will help identify other conserved synaptic molecular building blocks. Furthermore, this type of functional comparison across species will also identify structural domains added during evolution in correlation with increased complexity, shedding light on mechanisms underlying cognition and brain diseases.