Shimada Y et al. (2023) Biomolecules "Spermiogenesis in Caenorhabditis elegans: An Excellent Model to Explore the Molecular Basis for Sperm Activation."

Kanazawa-Takino N, Nishimura H, Shimada Y

[Biomolecules, 2023]

<i>C. elegans</i> spermiogenesis converts non-motile spermatids into motile, fertilization-competent spermatozoa. Two major events include the building of a pseudopod required for motility and fusion of membranous organelles (MOs)-intracellular secretory vesicles-with the spermatid plasma membrane required for the proper distribution of sperm molecules in mature spermatozoa. The mouse sperm acrosome reaction-a sperm activation event occurring during capacitation-is similar to MO fusion in terms of cytological features and biological significance. Moreover, <i>C. elegans fer-1</i> and mouse <i>Fer1l5</i>, both encoding members of the ferlin family, are indispensable for MO fusion and acrosome reaction, respectively. Genetics-based studies have identified many <i>C. elegans</i> genes involved in spermiogenesis pathways; however, it is unclear whether mouse orthologs of these genes are involved in the acrosome reaction. One significant advantage of using <i>C. elegans</i> for studying sperm activation is the availability of in vitro spermiogenesis, which enables combining pharmacology and genetics for the assay. If certain drugs can activate both <i>C. elegans</i> and mouse spermatozoa, these drugs would be useful probes to explore the mechanism underlying sperm activation in these two species. By analyzing <i>C. elegans</i> mutants whose spermatids are insensitive to the drugs, genes functionally relevant to the drugs' effects can be identified.

Lee JH (2022) Exp Neurobiol "Invertebrate Model Organisms as a Platform to Investigate Rare Human Neurological Diseases."

Lee JH

[Exp Neurobiol, 2022]

Patients suffering from rare human diseases often go through a painful journey for finding a definite molecular diagnosis prerequisite of appropriate cures. With a novel variant isolated from a single patient, determination of its pathogenicity to end such "diagnostic odyssey" requires multi-step processes involving experts in diverse areas of interest, including clinicians, bioinformaticians and research scientists. Recent efforts in building large-scale genomic databases and <i>in silico</i> prediction platforms have facilitated identification of potentially pathogenic variants causative of rare human diseases of a Mendelian basis. However, the functional significance of individual variants remains elusive in many cases, thus requiring incorporation of versatile and rapid model organism (MO)-based platforms for functional analyses. In this review, the current scope of rare disease research is briefly discussed. In addition, an overview of invertebrate MOs for their key features relevant to rare neurological diseases is provided, with the characteristics of two representative invertebrate MOs, <i>Drosophila melanogaster</i> and <i>Caenorhabditis elegans</i>, as well as the challenges against them. Finally, recently developed research networks integrating these MOs in collaborative research are portraited with an array of bioinformatical analyses embedded. A comprehensive survey of MO-based research activities provided in this review will help us to design a wellstructured analysis of candidate genes or potentially pathogenic variants for their roles in rare neurological diseases in future.

Berks M (1995) Genome Res "The C. elegans genome sequencing project. C. elegans Genome Mapping and Sequencing Consortium."

Berks M

[Genome Res, 1995]

Caenorhabditis elegans, a free-living nematode worm, has proved a particularly useful model organism for studying the anatomy, behavior, genetics, and development of a metazoan. It also has one of the smallest genomes of the higher eukaryotes (100 Mb distributed over six chromosomes), making it an ideal candidate for detailed molecular analysis. The C. elegans genome project began over 10 years ago and is a collaberative effort between two laboratories (St. Louis, MO, USA and Cambridge, UK), with the ultimate aim of mapping and sequencing the whole of the 100-Mb genome. The consortium has now completed the sequence of approximately one-fifth of the genome and plans to have sequenced more than half the genome before the end