During development, each neuron in the human brain must establish the correct identity and send its axon to the correct target.  We have found that the developmental anatomy of human cranial motor neurons, which originate in the brainstem and send axons to innervate the cranial muscles, is stereotypical, tractable, and conserved in model organisms, thus providing a beautiful paradigm for more complex neurodevelopmental processes. We study aberrant cranial motor neuron development by identifying human congenital disorders of eye and face movement, defining their genetic etiologies, and uncovering their molecular pathways and disease mechanisms. We also study normal cranial motor neuron development in mouse and zebrafish.

Major projects in the lab include (1) interpretation of >900 whole genome sequences from families with congenital disorders of eye and face movement, focusing on noncoding and structural variation as well as coding variants; (2) functional and mechanistic studies of genetic variants and their normal and abnormal proteins using mouse and zebrafish modeling, stem cell differentiation to the cell types of interest, and in vitro approaches, (3) studies of embryonic wildtype and mutant cranial motor neurons through single cell RNA sequencing, in situ studies, and mouse and zebrafish gene manipulations. These studies will define: how these motor neurons acquire distinct identities, form cranial nuclei and subnuclei, and target specific cranial musculature; how these processes are disrupted in human development to result in birth defects; and why these motor neurons are selectively vulnerable to or spared in specific neurodevelopmental and neurodegenerative disorders.