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Updated: Apr 28, 2026

Author Spotlight: Optimizing the Neurovascular Development of Human Brain Organoid in Chick Embryo
Published on: February 16, 2024
Whole organism 3D mapping reveals universal branching topology and biophysical optimization governs vascular and
André Forjaz1,2, Marco Costa1,2,3, Catarina Oliveira1,2,4
1Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD.
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.
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