Whole organism 3D mapping reveals universal branching topology and biophysical optimization governs vascular and nervous system development

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.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-04-13
DOI
https://doi.org/10.64898/2026.04.10.717729
Primary Topic
Plant and Biological Electrophysiology Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Whole organism 3D mapping reveals universal branching topology and biophysical optimization governs vascular and nervous system development

André Forjaz, Matthieu Wyart, Ashley Kiemen, Sean X. Sun et al.
bioRxiv (Cold Spring Harbor Laboratory)
Plant and Biological Electrophysiology Studies
article

Whole organism 3D mapping reveals universal branching topology and biophysical optimization governs vascular and nervous system development

André Forjaz, Matthieu Wyart, Ashley Kiemen, Sean X. Sun, Jamie O. Lo, Gabriel S. Bever, Marjorie R. Grafe, Vasco Queiroga, Lucie Dequiedt, Saurabh Joshi, Paul A. Gensbigler, Brice Menard, Marco Costa, William Foster, Catarina Oliveira, Denis Wirtz, Owen J McCarty
article en

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.

bioRxiv (Cold Spring Harbor Laboratory)
Santa Fe Institute (US), Johns Hopkins University (US), Oregon Health & Science University (US), Johns Hopkins Medicine (US), Instituto Superior de Gestão (PT), Instituto Superior Técnico (PT)
National Science Foundation, Johns Hopkins University, Fundação Luso-Americana para o Desenvolvimento, National Institutes of Health, Instituto Superior Técnico
Openalex Percentile: Top 28%
Plant and Biological Electrophysiology Studies
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