Linking developmental trajectories to neural circuit function in the Drosophila visual motion detection system

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To form brain circuits that serve behavior, neurons navigate a developmental trajectory from neural progenitors to functional modality-specific circuits. How this developmental trajectory endows neurons with identity and functional properties is an unsolved problem of relevance to health and disease. We use the Drosophila visual-motion sensitive system to investigate this question. The direction-selective motion-sensitive T4/T5 neurons are a powerful model to understand (1) how direction selectivity is achieved to tune T4/T5 neurons to four cardinal directions and (2) how the corresponding neuronal subtypes are specified. Findings from our labs suggest a need to revisit the current paradigm linking the specification of only four functional T4/T5 subtypes to a predetermined number of progenitor divisions: The Hassan lab demonstrated transient progenitor amplification, potentially leading to more T4/T5 cells than expected, and the Silies lab showed that there are six functional subtypes encoding optic flow patterns. Together, our discoveries suggest that transient amplification followed by functional specialization and neuronal elimination provide a developmental basis for the six functional types relevant for behavior. We will test this hypothesis and elucidate how development generates neurons with functional properties. Our combination of expertise will unravel the temporal trajectory of how the stereotyped T4/T5 cell number and functional specialization is established from a variable starting population of progenitors. Functional analysis of six subtypes projecting to four anatomical layers makes specific predictions about T4/T5 connectivity patterns to upstream and downstream optic flow neurons that will be explored using a unique combination of genetic tools and connectomics available in Drosophila. Our work will elucidate to what extent developmental mechanisms instruct functional neural circuit properties ultimately tuned to serve animal behavior.