Pei Zhang, Xiangchuan Wang, Tina Thuy N Nguyen Hoang, Guoye Guan
According to the strain distribution record from the Caenorhabditis Genetics Center (CGC) presented at the 25th International Worm Meeting in 2025, approximately 8,000 laboratories across 80 countries use these animals in their research. Establishing a sustainable culture and maintenance platform is essential for generating first-hand data on worm behaviors, particularly in laboratories with limited experience or resources. Here, using Caenorhabditis elegans as an example, we present a practical protocol for new researchers to establish basic worm-handling and -imaging workflows. We then describe procedures for collecting normal and perturbed C. elegans samples at selected early developmental stages for microscopic imaging. The imaging targets include germ cell development (mitosis and meiosis), prefertilization oocytes, oocyte-sperm pronuclear migration and fusion, pseudocleavage, and embryonic development (mitosis) that gives rise to the organism. Although embryonic and whole-organism imaging is straightforward, we provide enhanced guidelines and technical tips to facilitate precise germline and embryo dissection, rapid sample collection, mounting, timelapse imaging, and basic image analysis.