New atlas maps how the vascular network of mouse's brain grows after birth

Scientists have made a major advance in developmental neuroscience, creating the very first detailed atlas of how the vascular network of a mouse's brain grows after birth. Their study is published in Cell.

Co-led by Alexandre Dubrac, a researcher at the Centre de recherche Azrieli du CHU Sainte‑Justine and professor at Université de Montréal, the study was carried out in close collaboration with the laboratory of Nicolas Renier at the Paris Brain Institute.

It reveals that blood vessels in the brain don't simply develop in parallel with neurons.

Instead, their growth follows a dynamic, multi‑phase trajectory that varies across brain regions and is tightly linked to the maturation of neural circuits—granting blood vessels an active role in brain construction after birth.

"We knew that neurons undergo extensive changes after birth, but we understood far less about how blood vessels adapt to these transformations," said the study's co-first author Mathilde Bizou, a PhD student in Dubrac's lab.

"This atlas finally provides a comprehensive view of this essential dynamic."

A vital yet still mysterious network

Although it represents only a small fraction of body weight, the brain alone consumes about 20 per cent of the body's available oxygen and energy. Meeting this high demand depends on a dense and finely organized network of blood vessels responsible for delivering oxygen and nutrients to neurons.

At birth, this vascular network is still immature. Yet it is precisely after birth that the brain undergoes major transformations: it grows rapidly, neural circuits are refined, and certain regions specialize based on sensory experience and environmental input.

Until now, researchers had very limited tools to track—over time and across the entire brain—how blood vessels adapt to these changes.

"We had very detailed maps of the adult brain, but far less information on how the vascular network is established after birth," said Dubrac. "It was a bit like trying to understand how a city functions without access to its road map."

To address this gap, Renier's team developed a three‑dimensional atlas based on a mouse model, enabling them to track—with unprecedented spatiotemporal precision—the development of the vascular network from birth to adulthood.

For their part, Dubrac's team generated and integrated spatiotemporal transcriptomic data, making it possible to link vascular architecture to dynamic molecular programs.

By combining these complementary areas of expertise, the study reconstructs the brain's entire vascular network and analyzes its evolution over time, both structurally and molecularly.

Three major phases of development

One of the study's main contributions is the identification of three successive phases in postnatal blood vessel development.

The first phase corresponds to coordinated growth, during which the vascular network and the brain increase in size in a relatively proportional manner. This stage ensures adequate baseline perfusion during the first days of life, comparable to the final months of human fetal development.

The second phase marks a major shift. During this period, blood vessels grow faster than the brain itself, leading to a marked densification of the vascular network. This stage, which may correspond to early childhood and school age in humans, coincides with so‑called "critical periods" of brain development, when neural circuits are formed, refined, and specialized, particularly in response to sensory activity.

Finally, a third phase corresponds to a period of stabilization and refinement of the vascular network, which could be associated with adolescence. During this stage, vascular architecture reaches a more mature organization while retaining some capacity for remodeling.

Vascularization not uniform

The study shows that vascular network development is not uniform throughout the brain.

These differences are not explained solely by a general increase in neuronal activity, but rather by the fact that certain brain regions emit specific signals that directly influence whether blood vessel growth continues or stops.

By cross‑referencing vascular density maps with gene expression profiles, the researchers discovered that these signals act as genuine guidance cues for the vascular network, indicating where—and to what extent—it should continue to develop.

When these signaling pathways are disrupted, blood vessels lose their guidance, become disorganized, and grow aberrantly.

These findings demonstrate that the vascular network does not merely passively accompany brain development; it depends closely on communication with neuron, the scientists say.

This interaction is particularly critical during the second phase of postnatal development, a period when neuronal activity intensifies and tight coordination between the two systems becomes decisive for the brain's fine‑scale organization.

Probing childhood disorders and diseases

Beyond its fundamental contribution, the atlas provides an essential starting point for studying various disorders—including autism—as well as certain cerebrovascular diseases that emerge or originate during childhood, the researchers believe.

"Having a reference map of normal development will now allow us to compare what happens when this process is disrupted," said Dubrac.

"We will be able to better understand whether—and how—a mismatch between neuronal development and vascularization contributes to the vulnerability of specific brain regions."

He argued that the developing brain should now be thought of as a deeply neurovascular system, in which blood vessels play an active role in brain health, on a par with neurons themselves.