Genetic tuning of ipRGC subtype identity to shape visual behavior
The distinct blend of molecular and cellular features that define neuronal subtype identity are central to shaping how individual subtypes impact animal behavior. The diversity of the mammalian nervous system is vast — the retina alone contains over 100 neuronal subtypes. Yet, the genetic processes giving rise to this stunning structural and functional diversity remain poorly understood. Here, we uncover a graded expression pattern of the transcription factor Brn3b that tunes and maintains multiple, subtype-defining transcriptional and morphophysiological features of the melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). Disruption of this Brn3b gradient causes the transcriptional and morphophysiological identity of ipRGC subtypes to begin to converge, leading to dysfunction in multiple ipRGC-dependent behaviors. These findings show that a single transcription factor gradient can tune a diverse array of features to shape neuronal identity and circuit function to drive behavior. Overall design: Retina from Brn3b conditional knockout (Brn3bcKO) mice expressing Rpl22-HA in ipRGCs or control mice were subjected to translating ribosome affinity purification (TRAP) followed by library preparation using the Smart-seq3 protocol. RNA libraries were sequenced on the Illumina NextSeq 550 platform to obtain 37 bp paired-end reads. Two to four biological replicates were performed for all conditions.