Federal Grant Award Summary

The National Institute of Neurological Disorders and Stroke (NINDS) awarded Columbia University's Health Sciences Division a $644,965 Project Grant (CFDA 93.853: Extramural Research Programs in the Neurosciences and Neurological Disorders) effective February 1, 2026, through January 31, 2031. This research initiative investigates phylogenetic differences in motor neuron development between humans and mice using human induced pluripotent stem cell (hiPSC) differentiation. The project employs high-temporal resolution single-cell expression analysis to elucidate mechanisms underlying the prolonged and enhanced neurogenesis observed in the human spinal cord compared to rodent models, with particular focus on identifying human-specific ventral progenitor motor neurons (VPMNs) and their role in generating increased numbers of motor neurons enriched for limb innervation subtypes.

The research deliverables address four key scientific questions designed to advance understanding of human central nervous system development and motor neuron specification. Specifically, the project evaluates the necessity and sufficiency of NKX2-2 expression in activating the VPMN program, investigates evolutionary changes in the OLIG2 regulatory system permitting human-specific co-expression patterns, examines the contribution of elevated Notch signaling to VPMN specification and delayed neurogenesis, and characterizes motor neuron subtype diversity generated by VPMNs versus classical progenitor motor neurons. The anticipated outcomes are expected to provide molecular and cellular insights that may inform improved motor neuron disease models and therapeutic development strategies.