Biologists have recently gained new understanding of a long-standing mystery in biology: how complex organisms develop from a single fertilized cell. By creating a new ‘gene atlas’ using 4-D imaging, the researchers have gained unprecedented insights into the process of embryonic development unfolding.
Even though the Human Genome Project announced the completion of sequencing 20,000 human genes over 20 years ago, scientists are still striving to comprehend how fully developed beings emerge from the basic genetic instructions.
Biomedical research to understand how disorders can take hold in the earliest stages of development has been ongoing.Researchers from the University of California San Diego have gained new insights into the process of embryonic development by studying a simple model organism. The study, led by School of Biological Sciences scientist Rebecca Green and Professor Karen Oegema, focused on how genes work during embryonic development in the roundworm Caenorhabditis elegans (C. elegans), providing a detailed understanding of the process. Despite its small size, C. elegans has been widely used by biologists as a research tool.The biology of the worm, C. elegans, is similar to that of higher organisms like humans, making it a valuable research model for scientists. A collaborative team of researchers has compiled a “genetic atlas” of the worm after a decade of work, and their findings are published in the journal Cell. According to Green, the lead author of the paper, studying these genes in a simple organism like C. elegans can provide valuable insights into their functions in more complex organisms such as humans. Despite being studied in C. elegans, the majority of genes analyzed are also found in humans, making this research relevant to human biology.The scientists created a new system to analyze the function of genes necessary for embryonic development – the transformation of a fertilized egg into a multi-tissue organism. They used 4-D imaging to carefully monitor the function of each gene at every stage of embryogenesis, including the determination of cell identity and the formation of tissues. This monitoring was done using a technique called “computer vision,” and they found that many of these genes are linked to human developmental disorders.To monitor the progress of development, researchers kept a close eye on specific characteristics such as the number of cells in each tissue. They also closely monitored the weight, location, and structure of the tissues within the growing organism.
In order to gain a comprehensive understanding of the function of nearly 500 genes that play a crucial role in the development of embryos, the researchers systematically disabled the function of each gene individually. This approach allowed them to categorize genes into common groups, revealing the function of each gene through their associations. This process is similar to automated facial recognition, where images with similar features are grouped together. Through this rigorous analysis, A team of researchers used a collection of nearly 7,000 4-D embryogenesis movies to create unique “fingerprints” for individual genes. These fingerprints helped them understand the roles that genes play in embryogenesis, such as controlling the formation of tissues like muscle or skin. Oegema, a faculty member in the Department of Cell and Developmental Biology, stated that their approach correctly classifies gene functions, identifies functions for poorly characterized genes, and describes new gene and pathway relationships.The senior author of the paper explained, “Many genes that were previously thought to have ordinary functions have been discovered to play important roles that were not fully recognized.” Along with the publication in Cell, the extensive data gathered from the study led to the creation of a new online resource where all of the information is stored. This resource, called PhenoBank, now provides access to the genetic atlas that was developed during the research. The approach used in the study resulted in unexpected insights into the specialization of metabolic pathways during embryonic development and uncovered intriguing new connections between various molecular mechanisms involved in gene regulation.”Coauthor of the paper, Professor Arshad Desai, mentioned that the researchers are expanding their study beyond the 500 genes covered in the Cell study. They are now focusing on completing the entire set of 2,000 C. elegans genes that are involved in embryogenesis.
Desai emphasized the significance of their approach in addressing one of the most challenging problems in biology. He highlighted the complexity of how a single cell with a genome containing approximately 20,000 genes, similar to humans, is capable of developing into a complete organism.
The authors of the paper included Rebecca Green, Renat Khaliullin, Zhiling Zhao, Stacy Ochoa, Jeffrey Hendel, and Tiffany.-Lynn Chow, HongKee Moon, Ronald Biggs, Arshad Desai, and Karen Oegema express their gratitude to Tony Hyman and the Scientific Computing group at Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) for their assistance in building PhenoBank.
