C. elegans in Neurosciences

C. elegans in Neuroscience

C. elegans is a unique model for dissecting molecular events in neuro development. Soon after being introduced into the model, C. elegans was mapped at the level of genes, cells, and synapses, providing a key breakthrough in neurodevelopmental research with complete cell lineage, sequencing genomes, and linker. Its nervous system is composed of 5000 synapses, 302 neurons, 387 male neurons, 50 personality-sharing endothelial glia, and 6 related mesothelial glial cells and other subcutaneous cells. The discovery process is long and complicated.

Fig.1 The development process of C. elegans in neurodevelopment. (Rapti, 2020)

C. elegans was the first multicellular organism to sequence its genome. Its genome sequencing and subsequent gene mapping methods can identify all mutations that damage the development of the nervous system. Neural development proceeds through core processes such as nerve cell generation and differentiation, pathfinding, target selection and connection. Research on C. elegans revealed the principles that shape the surprising complexity of the nervous system.

Fig.2 The main developmental process of C. elegans nervous system formation. (Rapti, 2020)

Key Discoveries Based on C. elegans

• Alzheimer's disease (AD)

In 1993, the first presenile protein was discovered in C. elegans. Two years later, mutations in the human presenilin-1 gene were associated with early-onset familial AD.

• Diabetes Type 2

In 1997, genetic studies of C. elegans identified negative regulators of the insulin signaling pathway. One of the genes, daf-16, encodes a homologous gene of the C. elegans forkhead transcription factor FOXO70. Five years later, the loss of FOXO function rescued the diabetic phenotype of insulin-resistant mice.

• Depression

The antidepressant fluoxetine has been shown to increase the energy signal of serotonin by inhibiting the serotonin reuptake transporter SERT4 of C. elegans.

Although in most cases, the results of C. elegans phenotype research cannot be directly translated into human pathology, C. elegans analysis simulates some significant features of human pathology from multiple angles. These helps clarify the underlying molecular mechanisms of human diseases and provide new methods for treatment strategies.

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References

1. Rapti, G.; A perspective on C. elegans neurodevelopment: from early visionaries to a booming neuroscience research. Journal of Neurogenetics. 2020, 34(3-4): 259-272.
2. Kaletta, T.; Hengartner, M.O. Finding function in novel targets: C. elegans as a model organism. Nature reviews Drug discovery. 2006, 5(5): 387-399.