During the earliest stages of life, a tiny embryo undergoes an extraordinary transformation, laying out the plan for its entire body structure. This process, known as embryonic axis formation, ensures that essential organs and tissues develop in the correct locations. Experts have long investigated the signals that direct this process, particularly the role of maternal factors that set the foundation for proper development. One of the most important of these factors is the Huluwa protein, which plays a key role in triggering essential communication pathways within cells. These pathways allow cells to send and receive signals that guide their function and position in the developing embryo. While scientists have known about Huluwa’s role in development, the exact way it functions has remained unclear—until now.
Professor Jing Chen from Sichuan University and colleagues have made a major advancement in understanding how vertebrate embryos establish their body axes, a crucial step in early development. Researchers have pinpointed a specific molecular switch in the Huluwa protein that controls this process, providing valuable insights into the complex mechanisms guiding embryonic growth. This discovery sheds new light on how β-catenin signaling, a vital communication system in cells that regulates gene activity, is controlled during axis formation.
Professor Chen’s findings, published in Nature Communications, reveal that a single amino acid, Serine 168, in the Huluwa protein is essential for activating β-catenin signaling. Amino acids are the building blocks of proteins, and Serine 168 acts as a critical site for regulation. This process ultimately directs axis formation in developing zebrafish and Xenopus embryos, ensuring that the body is properly structured.
Professor Chen’s team discovered that changing Serine 168 to a different amino acid, alanine, completely stopped Huluwa from carrying out its function. This alteration weakened the protein’s ability to attach to other important molecules, specifically Tankyrase 1 and Tankyrase 2, which are enzymes that help control the stability of proteins involved in cell signaling. As a result, a crucial protein called Axin, which plays a role in regulating β-catenin levels, was not broken down as needed, leading to a disruption in β-catenin signaling. This finding underscores how vital Serine 168 is in setting off a chain reaction that ensures the proper formation of the body’s layout. Additionally, 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, turning proteins on or off to regulate cell processes and help Huluwa carry out its function in axis formation.
“This research demonstrates that phosphorylation, the addition of a phosphate group to a protein, at Serine 168 is crucial for Huluwa’s role in β-catenin signaling and body axis formation,” explained Professor Jing Chen. “By identifying this molecular switch, we now have a deeper understanding of how Huluwa is controlled at a cellular level, which is essential for ensuring normal embryonic development.”
The significance of these findings goes beyond early development. Understanding how the body’s blueprint is established could have broader applications in medicine, particularly in regenerative therapies, which involve repairing or replacing damaged tissues, and conditions that affect developmental processes. The ability to adjust β-catenin signaling through targeted molecular modifications could pave the way for new medical treatments, especially in cases where normal growth pathways are disrupted.
Professor Chen’s research into Huluwa’s phosphorylation has provided a clearer picture of how embryos develop their structural plan. Future studies may explore whether similar molecular switches exist in other organisms or if this mechanism can be applied to related biological processes. As scientists continue to uncover the complex interactions between proteins that shape early life, this discovery marks an important step forward in developmental biology.
Journal Reference
Li Y., Yan Y., Gong B., Zheng Q., Zhou H., Sun J., Li M., Wang Z., Li Y., Wan Y., Chen W., Qi S., Mo X., Meng A., Xiang B., Chen J. “A Huluwa phosphorylation switch regulates embryonic axis induction.” Nature Communications, 2024. DOI: https://doi.org/10.1038/s41467-024-54450-4
About the Author
Jing Chen, Ph.D, Professor: Principal Investigator in the Department of Pediatric Surgery and Laboratory of Pediatric Surgery at West China Hospital, Sichuan University, Chengdu, China.
His research primarily focuses on developmental biology, particularly the mechanisms regulating axis formation, patterning and morphogenesis. Dr. Chen’s work uses zebrafish/mouse models and advanced biology techniques to unravel the complex regulatory networks that govern developmental processes, with implications for understanding congenital disorders and developmental biology at large.Dr. Chen’s pioneering work in developmental biology has yielded great discoveries, with landmark studies published in Science, Nature Communications, Human Genetics, Journal of Genetics and Genomics, Journal of Biological Chemistry, and Molecular Biology and Evolution. These seminal contributions have fundamentally advanced our understanding of three-dimensional morphogenetic regulation.
