Biologist, Know Thy Cells - A Colorful Barcoding Method to ID Cell Types, their Fate, and Decode Brainwide Communication


This seminar will be held on Microsoft Teams. Please join with your video off and mikes muted. Email hod-pa@dpag.ox.ac.uk for more details.

A major challenge in biological imaging is resolving cell identities. These are necessary for determining cell-specific protein expression and function, the effect of transcription factors on cell fate, and the contribution of individual neurons to brainwide activity and behavior. Present methods are limited to a piecemeal approach, using multiple strains to identify a few cell types at a time. I introduce a new method and software that can identify many cell types, and in some cases all neurons, in vivo using a single strain. My method combines cell reporters with five distinguishable fluorescent proteins to create unique, stereotyped color codes that identify cell types. I illustrate this in C. elegans, engineering a multicolor transgene called NeuroPAL (a Neuronal Polychromatic Atlas of Landmarks), to create an identical colormap in all worms that uniquely identifies every neuron, showcasing three applications. First, I identify the neuronal expression patterns of all metabotropic receptors for acetylcholine, GABA, and glutamate, thus completing a map of this communication network. My findings indicate that second-messenger systems are the primary means of GABA communication in worm, and further suggest widespread extrasynaptic GABA signaling. Second, I analyze the conserved transcription factor EOR-1/PLZF and, despite its ubiquitous expression, uncover a precise role in neuronal fate. Third, I identify brainwide codes for gustatory and olfactory stimuli. My findings show a complex code that challenges the present view that global neuronal activity is simply low dimensional. To facilitate the workflow, I present semi-automated cell identification software and optimal-coloring software to apply the same method in other tissues and organisms. Lastly, I discuss future applications: investigating how whole-nervous-system activity is remodeled to change behavior during early development, sexual maturation, in response to environmental stress, and even across 15+ million years of evolutionary divergence.