Researchers demonstrated that internal cellular transport pathways direct cavity development in human embryonic models, according to a peer-reviewed study published in Nature Communications. The work centers on epiblast lumen formation, a structural step during human embryo implantation that begins with an apical compartment called an apicosome. Material for the apicosome comes partly from endocytosis.
Tests using human pluripotent stem cell-derived models showed that apicosome generation prompts a temporary expansion across multiple stages of the endo-lysosomal pathway. Early endosomes, late endosomes, and lysosomes all enlarge transiently during this transition. In addition, the cells assemble hybrid compartments that combine physical features from both early and late endo-lysosomal phases.
Two regulatory proteins govern these membrane shifts. The researchers found that the RAB GTPases RAB35 and RAB7 are required for proper apicosome formation and lumen morphology. Membrane remodeling dependent on these two GTPases serves as a primary mechanism driving apical membrane morphogenesis in the human epiblast model.
Scientists from the Medical College of Wisconsin and the University of Michigan Medical School conducted the study. The team sourced experimental vectors and constructs from researchers at Kyoto University, McGill University, and Rockefeller University, while using the University of Michigan Proteomics Resource Facility during the project.
National Institutes of Health grants R01-HD098231, R01-HD102496, and R01-GM129255 funded the research alongside Medical College of Wisconsin start-up funds. Nature Communications accepted the paper on August 17, 2026, following submission on August 18, 2025, and published it on August 27, 2026.
