Developmental dynamics and axonal transport of cerebral cortex projection neuron mRNAs in vivo

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Abstract
Appropriate development of long-range nervous system circuitry requires dynamic regulation of subcellular mRNA localization, but little is known about how specific neuron subtypes control this critical process in vivo . Here, we employ an integrated genetic and temporally controlled approach to investigate in vivo developmental mRNA dynamics in somata and axons of a prototypical cerebral cortex projection neuron subtype, callosal projection neurons (CPN), which connect the cortical hemispheres to integrate sensorimotor information, and regulate high-level associative cognition and behavior. We identify cis-regulatory elements that are associated with mRNA turnover in CPN somata, including specific 3’ untranslated regions (UTRs), and elucidate distinct modes of axon transport in CPN axons for function-specific mRNA classes. Together, these findings elucidate how developing CPN control subcellular mRNA localization, and how dysregulation of these processes might lead to neurodevelopmental and/or neurodegenerative disorders. More broadly, this work identifies general mRNA localization mechanisms that likely function across projection neuron subtypes, and in other polarized cells.
Funding Information
  • Allen Institute (ADI11855)
  • National Science Foundation (280932)
  • National Science Foundation (1764269)

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