Research

At NeuroPlaNe Lab, we are interested in how the brain is built and refined over time — from early development to later stages of maturation. A central question that motivates our work is why many findings obtained in rodent models do not fully translate to the human brain. Differences in size, structure, and developmental timing are likely to play a major role, and understanding these differences is essential if we want to move towards more realistic models of brain function and disease.

To address this, we combine the study of human brain development with comparative approaches and high-resolution structural analysis. Our goal is to understand how neural progenitors generate cellular diversity, how neurons migrate and mature, and how some populations remain immature for extended periods before integrating into functional circuits.


1. Human brain development and progenitor dynamics

Understanding how cellular diversity emerges in the human brain

A major focus of the lab is the developing human brain, particularly the ventricular and periventricular regions where neural progenitors reside. These germinal zones are responsible for generating the wide variety of neuronal and glial cell types found in the adult brain.

We are especially interested in the ganglionic eminences — medial, lateral, and caudal — which give rise to key neuronal populations in the forebrain. Our work examines how radial glia and intermediate progenitors are organized, how they proliferate, and how newly generated neurons migrate and populate different brain regions.

One of the key issues we address is how these processes differ from what has been described in rodents. In humans, progenitor dynamics, migratory routes, and developmental timing show important differences that are still not fully understood. These differences are likely to be critical for the expansion and specialization of the human brain, and may also help explain why disruptions in early development can lead to neurodevelopmental and psychiatric disorders.

By combining molecular approaches with histological and ultrastructural analysis, we aim to build a more precise picture of how the human forebrain is assembled.


2. Immature neurons, prolonged maturation, and brain plasticity

How delayed maturation may support long-term plasticity

Another central line of research in the lab focuses on neuronal populations that remain immature well beyond early development. These cells, often identified by markers such as DCX, are present in different brain regions and challenge the classical view that neurons rapidly reach full maturity after they are generated.

Rather than being continuously produced from stem cells, many of these neurons appear to follow a prolonged maturation process. They can remain in a partially differentiated state for extended periods, potentially acting as a reservoir that can be recruited later and integrated into existing circuits.

We are interested in how these cells are generated, what regulates their delayed maturation, and how they interact with their surrounding environment. Using both human tissue and comparative models, we study their cellular features, their spatial organization, and the timing of their maturation.

Understanding these populations may provide new insights into mechanisms of brain plasticity, but also into vulnerability. Alterations in these processes have been linked to conditions such as epilepsy, autism spectrum disorder, and other neurodevelopmental disorders.


3. Comparative organization of the paralaminar amygdala

A model system for late-maturing neurons

The paralaminar nucleus of the amygdala is a key system in our research. This region is particularly intriguing because it contains a large population of immature neurons that persist after birth and gradually mature over time.

In primates, the paralaminar nucleus shows a distinctive developmental profile compared to the rest of the amygdala, suggesting that it may play a role in the refinement of emotional and associative circuits. However, its origin, organization, and function are still not well understood.

We use this region as a model to study prolonged neuronal maturation in a more defined anatomical context. A major part of our work involves determining whether comparable structures exist in more accessible species, such as the mouse, and how this system varies across lissencephalic and gyrencephalic brains, including pigs and ferrets.

Our approach combines molecular characterization, ultrastructural analysis, and developmental studies to understand how these neurons are generated, how they mature, and how they integrate into existing circuits.


Funding

Our research is supported by the Generalitat Valenciana through the Prometeo Program (CIPROM2023-053) and by the Universitat de València.

Learn more about the project