Molecular signatures and cellular diversity during mouse habenula development
Lieke L. van de Haar,
Danai Riga,
Juliska E. Boer,
Oxana Garritsen,
Youri Adolfs,
Thomas E. Sieburgh,
Roland E. van Dijk,
Kyoko Watanabe,
Nicky C.H. van Kronenburg,
Mark H. Broekhoven,
Danielle Posthuma,
Frank J. Meye,
Onur Basak,
R. Jeroen Pasterkamp
Affiliations
Lieke L. van de Haar
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands
Danai Riga
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands
Juliska E. Boer
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands
Oxana Garritsen
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands
Youri Adolfs
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands
Thomas E. Sieburgh
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands
Roland E. van Dijk
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands
Kyoko Watanabe
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, 1081 Amsterdam, the Netherlands
Nicky C.H. van Kronenburg
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands
Mark H. Broekhoven
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands
Danielle Posthuma
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, 1081 Amsterdam, the Netherlands
Frank J. Meye
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands
Onur Basak
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands
R. Jeroen Pasterkamp
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 Utrecht, the Netherlands; Corresponding author
Summary: The 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 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.
