Molecular Signatures and Cellular Diversity During Mouse Habenula Development

Author:

van de Haar Lieke L.ORCID,Riga DanaiORCID,Boer Juliska E.ORCID,Adolfs YouriORCID,Sieburgh Thomas E.,van Dijk Roland E.,Watanabe KyokoORCID,van Kronenburg Nicky C.H.,Broekhoven Mark H.,Posthuma DanielleORCID,Meye Frank J.ORCID,Basak OnurORCID,Pasterkamp R. JeroenORCID

Abstract

SUMMARYThe habenula plays a key role in various motivated and pathological behaviors and is composed of molecularly 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 embryonic 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 previously uncharacterized subtype of Cartpt+ habenula 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.

Publisher

Cold Spring Harbor Laboratory

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