The nervous system at single-cell resolution: Quantitative microscopy and the study of neurodevelopment in vivo
How individual cells communicate and coordinate to produce organized tissues during embryonic development remains a field of active study. Advances in 3D fluorescence microscopy and automated image analysis have enabled new approaches to the study of organism- and tissue-level phenomena with single cell resolution. By applying quantitative imaging methods in concert with classical genetic perturbations we have uncovered a novel, convergent function of two broadly conserved signaling pathways, the planar cell polarity pathway and the sax-3/Robo receptor, in regulating the morphogenesis of the C. elegans ventral nerve cord. More recently, we have developed a novel platform for real-time cell tracking and automated single-cell resolution perturbation to dissect fundamental mechanisms that guide the patterning of the nervous system. We demonstrated the power of this approach in several contexts: by dissecting the establishment of polarity in sensory hair cells of the zebrafish lateral line and by studying neuron-glia interactions in the morphogenesis of the C. elegans nervous system. We are now applying this platform in concert with next-generation microscopy modalities, advances in computer vision, and new optical methods for manipulating single neurons in vivo to build toward a complete and quantitative understanding of the development of the embryonic nervous system.