Stanford Psychiatry’s Sergiu Pasca Awarded Grant Examining Human Cellular Model of Midline Crossing to Study Developmental Neurological Disorders

We are pleased to announce that Stanford Psychiatry’s Sergiu Pasca, the Kenneth T. Norris, Jr. Professor of Psychiatry and Behavioral Sciences and Bonnie Uytengsu and Family Director of the Stanford Brain Organogenesis Program, has received a grant from the National Institute of Neurological Disorders and Stroke to examine the human cellular model of midline crossing to study developmental neurological disorders.

Multiple neurological disorders are associated with issues in establishing midline connectivity in the developing human nervous system - however, no models have been available to study the midline-guided axonal crossing.

In this project, Dr. Pasca and the study team plan to generate a novel model of the developmental processes underlying the spinal cord midline crossing of axons. To achieve this, they will generate and functionally characterize organoids that resemble the human floor plate, and then assemble them bilaterally with organoids resembling the dorsal spinal cord to derive midline assembloids and recapitulate midline crossing of human axons. They will then systemically apply this microphysiological system to study axon guidance defects following loss of neurodevelopmental disease genes.

“Progress in understanding neurological disorders has been hindered by a lack of access to live neural cells from patients for direct investigation,” says Dr. Pasca. “We will build a novel stem cell-derived human assembloid model of midline crossing to study how human axons develop in human central nervous system development, and plan to systematically apply this platform to understand the cellular phenotypes and molecular mechanisms of genetic neurological developmental disorders.”

Dr. Pasca leads the Pasca Lab, seeking to understand the rules that govern the assembly of the human brain and the molecular mechanisms that lead to neuropsychiatric disease. To achieve this, the laboratory has pioneered and applied neural organoid and assembloid technologies to make discoveries in fundamental and clinical neuroscience. Recent publications related to this work include “A framework for neural organoids, assembloids and transplantation studies” in the journal Nature, and “Generating human neural diversity with a multiplexed morphogen screen in organoids” published in the journal Cell Stem Cell.

More Information

Read more details about the project on NIH RePORTER.