Whole organism 3D mapping reveals universal branching topology and biophysical optimization governs vascular and nervous system development
Year: 2026
Type: preprint
Abstract: The vascular and nervous systems are transport networks essential for life, yet whether universal geometric and topological principles govern their formation remains unclear. The organism-wide molecular and biophysical coordination required to build and maintain these networks during embryonic development has inspired decades of theoretical work, offering predictions about their expected organization. However, the lack of complete three-dimensional (3D) data has limited validation to isolated structures, leaving whole-organism networks unexplored. Here, we developed a computational pipeline for whole-organism 3D imaging to reconstruct the complete vascular and nervous systems of rhesus macaque, mouse, and turtle embryos. Our analysis reveals that both networks share structural principles, including binary branching and scale-invariant bifurcation geometry, maintained across species and throughout development. Yet, from these shared rules emerge fundamentally different architectures. Vasculature exhibits fractal topology with a fractal dimension ~3, forming space-filling trees that prioritize proximity to every cell in the body. Nervous system networks exhibit a fractal dimension ~2, forming sheet-like arbors that prioritize electrical signal transmission. This architectural divergence originates from distinct biophysical constraints operating in bifurcations, where vascular junctions minimize energy expenditure while conserving fluid flow and nerve junctions maximize conduction velocity while conserving electrical current. These local optimization rules, iterated across generations, construct organism-wide networks governed by distinct physical constraints, revealing how evolution generated different solutions for fluid versus electrical transport.
Language: English
Subfield: Biophysics
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Johns Hopkins University, Fundação Luso-Americana para o Desenvolvimento, National Institutes of Health, Instituto Superior Técnico, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Shear stress Regulation of Endothelial Glycolysis via METTL3-mediated RNA m6A Modification, COLLABORATIVE RESEARCH: Integrative Approaches to the Turtle Body Plan: Evolutionary Origins of Structural Complexity in an Enigmatic Lineage, Novel Optical Imaging Approach to Study Neurovascular Coupling System, G5419800355, Three-dimensional maps of senescence in the human pancreas, G9000056679, G9000196955, G9000207249, G9000234658, G9000342207, Center for 3D Imaging in Cancer Cell Biology, Engineering self-propelled tumor-infiltrating CAR T cells using synthetic velocity receptors, HIPC Data Coordinating Center, SPORE in Ovarian Cancer, The Human Lung BioMolecular Multi-Scale Atlas Program (HuBMAP-Lung), Kidney single cell and spatial molecular atlas project - KIDSSMAP
OpenAlex ID: W7154423192