Neuronal subtype-specificity of ribosomal complexes during cerebral cortex circuit formation

Abstract

During brain development, immensely diverse subtypes of projection neurons establish precise long-range axonal projections, forming distinct functional circuits that control specific behaviors. While transcriptional regulation of circuit formation is increasingly well understood, the role of translational control remains poorly characterized, particularly how it might be specialized in distinct neuronal subtypes during establishment of long-range axonal projections. This dissertation investigates specialization of translational machinery - specifically ribosomes and their associated proteins (collectively called "ribosomal complexes") - between distinct subtypes of cortical projection neurons in vivo. Combining labeling of circuit-specific somata for purification by fluorescence-activated cell sorting, pulldown of ribosomal complexes, and ultra-low input proteomics, this research reveals distinct protein compositions of ribosomal complexes between two closely related subtypes with strikingly distinct axonal connectivity - cortical output “subcerebral PN” (SCPN) and interhemispheric “callosal PN” (CPN). These findings provide new insight into how translational control might contribute to the precise establishment of neural circuits during development, identify several candidate proteins for functional investigations of roles in translation and subtype-specific circuit formation, and contribute to understanding of how ribosomes are employed in distinct biological contexts.