Fetal Brain Development: Autism, Depression, Parkinson’s Origins
Unlocking Brain Growth: How Early Gene Activity Shapes Mental and Neurological Health
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New research reveals that genes linked to a wide range of brain disorders are active from the earliest stages of fetal development, offering new avenues for understanding and treating complex conditions.
A groundbreaking study by researchers at the Biomedical Informatics Research Program of the Hospital del Mar Research Institute, in collaboration with Pompeu Fabra University, has shed new light on the origins of neuropsychiatric and neurodegenerative diseases. By simulating the impact of nearly 3,000 genes associated with thes conditions on developing brain cells, the team discovered that many of these genes are already functional during the critical initial phases of fetal development.
Early Gene Function: The Foundation of Brain Health
The research focused on stem cells, the progenitor cells responsible for building the brain, including neurons and their supporting structures.The findings indicate that alterations in these genes during these nascent stages can have profound and lasting effects on brain development,potentially leading to mental disorders later in life.
“Scientists usually study the genes of mental illnesses in adults,” explains Dr. Nicola Micali,an associate researcher at dr. Pasko Rakic’s lab at Yale University and co-leader of the research. ”But in this work, we discovered that many of these genes already act during the early stages of fetal brain formation, and that their alterations can affect brain development and promote mental disorders later on.”
Studying this early period of brain development is notoriously challenging. To overcome this hurdle, the researchers employed a multi-faceted approach, combining data from both human and mouse brains, as well as in vitro cellular models.This extensive strategy allowed them to simulate the specific regulatory networks for each cell type involved in brain development.
Simulating Gene Impact on Progenitor Cells
the simulations allowed the scientists to observe how the activation or deactivation of genes linked to various brain diseases affected progenitor cells at different developmental stages. This granular analysis highlighted the crucial role of each gene in the emergence of alterations that underpin a wide spectrum of diseases.
The study’s scope is extensive, encompassing conditions such as microcephaly, hydrocephaly, autism, depression, bipolar disorder, anorexia, schizophrenia, Alzheimer’s, and Parkinson’s disease. In all these pathologies, the research identified genes that are involved in the earliest phases of brain development when neural stem cells are actively functioning.
Identifying Critical Temporal Windows and Cell Types
“We cover a wide spectrum of diseases that the brain can have and look at how the genes involved in these conditions behave in neural stem cells,” states Xoel Mato-blanco, a researcher at the Hospital del Mar Research Institute. he further emphasizes the study’s contribution: “The work identifies temporal windows and cell types where the action of these genes is most relevant,indicating when and where you should target the function of these genes.”
Implications for Disease Understanding and Treatment
This detailed understanding of gene function during early development is invaluable for deciphering the origins of diseases affecting the cerebral cortex.”Having this details is useful to understand the origin of diseases that affect the cerebral cortex, that is, how genetic alterations translate into these pathologies,” says Dr. Santpere.
By elucidating these mechanisms and the specific role of each gene in different diseases, the research opens up exciting possibilities for developing targeted therapies. This includes the potential for gene therapy and personalized treatments that can intervene at critical developmental junctures, offering new hope for individuals affected by a broad range of neurological and psychiatric conditions.
source: Hospital del Mar Medical Research Institute
Journal Reference: Mato-Blanco, X., et al. (2025). Early developmental origins of cortical disorders modeled in human neural stem cells. Nature Communications. doi.org/10.1038/s41467-025-61316-w