In the earliest stages of life, a tiny embryo undergoes extraordinary transformations, creating plans for the entire body structure. This process, known as the formation of the embryonic axis, ensures the development of essential organs and tissues in the right location. Experts have long investigated the role of maternal factors that guide this process, especially the role of maternal factors that lay the foundation for proper development. One of the most important factors is the Huluwa protein, which plays a key role in triggering basic communication pathways within cells. These pathways allow units to send and receive signals to guide their function and location in a developing embryo. Although scientists already know the role of Huluwa in development, the exact way it is still unclear, until now.
Professor Jing Chen from Sichuan University and colleagues has made significant progress in understanding how vertebrate embryos establish a body axis, a key step in early development. Researchers have pointed to specific molecular switches in Huluwa proteins that control this process, providing valuable insights into the complex mechanisms that guide embryo growth. This finding elucidates how β-catenin signaling is an important communication system in cells that regulate gene activity.
The findings published by Professor Chen in Natural Communications suggest that the single amino acid serine 168 in the Huluwa protein is crucial for activating β-catenin signaling. Amino acids are the basis of proteins, and serine 168 acts as a key site for regulation. This process ultimately guides the axis formed in the development of zebrafish and Xenopus embryos to ensure the body is structured correctly.
Professor Chen’s team found that changing serine 168 to a different amino acid Alanine completely prevented Huluwa from performing its functions. This change weakens the protein’s ability to attach to other important molecules, especially Tank Enzyme 1 and Tank Enzyme 2, which are enzymes that help control the stability of proteins involved in cellular signaling. As a result, a key protein called Axin plays a role in regulating β-catenin levels and is not broken down as needed, resulting in disruption of β-catenin signaling. This finding emphasizes how serine 168 ensures the correct formation of the body layout when setting up the chain reaction. In addition, the researchers identified several enzymes responsible for adding phosphate groups to proteins, such as cyclin-dependent kinase 16, cyclin-dependent kinase 2, and glycogen synthase kinase 3β. These enzymes act as molecular switches that turn the protein on or off to regulate cellular processes and help Huluwa play a role in axis formation.
“This study shows that adding phosphate groups to proteins at serine 168 is crucial for Huluwa’s role in β-catenin signaling and body axis formation,” explains Professor Jing Chen. “By identifying this molecular switch, we now have a deeper understanding of how Huluwa can be controlled at the cellular level, which is crucial to ensure normal embryonic development.”
The importance of these findings goes beyond early developments. Understanding how the body’s blueprint can be built that may have a wider application in medicine, especially in regenerative therapies, involves repairing or replacing damaged tissue and conditions that affect developmental processes. The ability to regulate β-catenin signaling through targeted molecular modifications may pave the way for new medical treatments, especially in cases where normal growth pathways are disrupted.
Professor Chen’s study of Huluwa’s phosphorylation provides a clearer understanding of how embryos develop their structural plans. Future research may explore whether similar molecular switches exist in other organisms or whether the mechanism can be applied to relevant biological processes. This discovery marks an important step in developing biology as scientists continue to uncover the complex interactions between the proteins that shape early life.
Journal Reference
Li Y., Yan Y., Gong B., Zheng Nature Communications, 2024. doi: https://doi.org/10.1038/s41467-024-54450-4
About the Author
Dr. Jing Chen, Professor: Principal researcher at the Department of Pediatric Surgery and Pediatric Surgery Laboratory of West China Hospital, Sichuan University, China.
His research focuses mainly on developmental biology, especially the mechanisms that regulate axis formation, pattern and morphogenesis. Dr. Chen’s work uses zebrafish/mouse models and advanced biological techniques to reveal complex regulatory networks that control developmental processes, which have a great impact on understanding congenital diseases and developmental biology. Chen’s pioneering work in pioneering biology has made great discoveries and has published landmark research. science,,,,, Journal of Natural Communication, Journal of Human Genetics, Genetics and Genomics, Journal of Biochemistry, and Molecular Biology and Evolution. These pioneering contributions fundamentally present our understanding of three-dimensional morphogenesis regulation.
