We study the gene networks driving neuronal diversity during brainstem development to uncover why only specific subsets are differentially affected in a given human neurologic disease. The brainstem controls multiple critical motor and sensory functions, including eye movements, facial expression, speech, hearing, proprioception, arousal, and breathing. Disruption of these functions can lead to profound deficits including in childhood social interaction. The anatomy and gene circuits in the brainstem are highly conserved in mice, providing an ideal model system to investigate neuronal specification and axon growth and guidance in both health and disease.
We combine neurodevelopmental tools, 3D imaging, multi-omics/bioinformatic approaches, molecular/synthetic biology, and mouse models of human disease to define developmental differences among various neuronal populations. Through a single cell and spatial transcriptomic atlas of developing motor neurons, we have identified unique genetic fingerprints of each motor neuron population, including novel markers of spatially and temporally distinct subpopulations that contribute to specific aberrant nerve branches in mouse models of childhood disorders. This work provides a new toolbox to study differential neuronal vulnerability in disease.