Improved Understanding of Human Brain Development and Disorders

New findings provide a better understanding of human brain development and potentially how birth defects and neurodevelopmental disorders arise. The findings also inform an approach for creating stem cell-derived tools to deliver neurotherapeutics.

Irvine, Calif., June 5, 2025 — The results of an experimental study have researchers at UC Irvine rethinking human brain development.

The study involved coming up with a simple way to grow special cells of the brain — choroid plexus epithelial cells (CPECs) — using starter cells (“stem cells”) in culture dishes. “Using this simple method and human tissues, we traced the origins of CPECs and their family tree during pregnancy,” says Ed Monuki, MD, PhD, professor and chair of Pathology & Laboratory Medicine. “It turns out that this family tree is more complex than expected, which forces us to rethink how CPECs and the choroid plexus support the developing human brain.”

A paper published online on June 3, 2025, in Nature Communications, describes the work.

Their discovery also suggests that CPECs are the earliest progeny of the original stem cells of the human brain known as neuroepithelial cells. “Scientists had believed that all CPECs were the same,” says Haley Masters, lead author and former PhD student in the Monuki Lab. “Our discovery indicates that this is not the case. In addition, brain stem cells can diversify into CPEC subtypes on their own, even in a lab dish.”

In addition to increasing our understanding of normal brain development, this discovery of CPEC subtypes also has implications for addressing birth defects and neurodevelopmental disorders. Examples include hydrocephalus and diseases such as choroid plexus tumors and cancers. “Our discovery should also advance our patented idea of using CPECs to deliver therapeutics to the brain via the fluid they produce (cerebrospinal fluid) rather than through the blood,” says Masters.

For even better models of human choroid plexus development, disease and neurotherapeutic delivery, the researchers are currently extending the method to make choroid plexus organoids and vascularized choroid plexus in collaboration with Quinton Smith, an assistant professor of chemical and biomolecular engineering at UC Irvine, with support from a pilot award from the Center for Neurotherapeutics.

“We also have multiple projects using the new system for disease modeling,” says Monuki. “These projects include modeling a developmental disorder that selectively affects CPECs, modeling aging-related CPEC pathologies that I see as a neuropathologist, and studying the developmental basis of brain aging and neurodegenerations such as Alzheimer’s disease.” These projects use patient-derived and gene-edited stem cells, in collaboration with the Induced Pluripotent Stem (iPS) Cell Core, established by UC Irvine’s Alzheimer’s Disease Research Center (ADRC) in the Sue and Bill Gross Stem Cell Research Center.

These studies should shed light on how certain gene mutations act through CPECs to impact or cause disease.

About the UC Irvine School of Medicine

Each year, the UC Irvine School of Medicine educates more than 500 medical students and nearly 150 PhD and MS students. More than 750 residents and fellows are trained at the UCI Medical Center and affiliated institutions. The School of Medicine offers multiple MD, PhD and MS degrees, and students are encouraged to pursue an expansive range of interests and options. The UC Irvine School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit medschool.uci.edu.