Molecular signatures and cellular diversity mouse habenula development

The habenula plays a key role in various motivated and pathological behaviors and is composed of molecu-larly distinct neuron subtypes. Despite progress in identifying mature habenula neuron subtypes, how these subtypes develop and organize into functional brain circuits remains largely unknown. Here, we performed single-cell transcriptional profiling of mouse habenular neurons at critical developmental stages, instructed by detailed three-dimensional anatomical data. Our data reveal cellular and molecular trajectories during em-bryonic and postnatal development, leading to different habenular subtypes. Further, based on this analysis, our work establishes the distinctive functional properties and projection target of a subtype of Cartpt+ habe-nula neurons. Finally, we show how comparison of single-cell transcriptional profiles and GWAS data links specific developing habenular subtypes to psychiatric disease. Together, our study begins to dissect the mechanisms underlying habenula neuron subtype-specific development and creates a framework for further interrogation of habenular development in normal and disease states.

Automated summary

This study reveals the cellular and molecular trajectories of habenular neuron development and organization into subtypes, as well as their distinctive functional properties and projection targets. It also links specific developing habenular subtypes to psychiatric disease, providing a framework for further investigation of habenular development in normal and disease states.