Molecular signatures and cellular diversity during mouse habenula development
van de Haar, Lieke L.; Riga, Danai; Boer, Juliska E.; Garritsen, Oxana; Adolfs, Youri; Sieburgh, Thomas E.; van Dijk, Roland E.; Watanabe, Kyoko; van Kronenburg, Nicky C.H.; Broekhoven, Mark H.; Posthuma, Danielle; Meye, Frank J.; Basak, Onur; Pasterkamp, R. Jeroen
(2022) Cell Reports, volume 40, issue 1, pp. 1 - 32
(Article)
Abstract
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
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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.
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Keywords: axon guidance, connectivity, CP: Neuroscience, development, electrophysiology, habenula, mouse, neuronal subtype, neurotransmitter, single-cell RNA sequencing, spatial expression, General Biochemistry,Genetics and Molecular Biology
ISSN: 2211-1247
Publisher: Cell Press
Note: Funding Information: We thank Dinos Meletis for input on our manuscript; Eric Turner for Brn3a-tauLacZ mice; and Kiochi Hashikawa, Garret Stuber, Michael Wallace, Bernardo Sabatini, Shristi Pandey, and Alexander Schier for sharing data. This research was supported by the Netherlands Organisation for Scientific Research ( ALW-VICI 865.14.004 to R.J.P.), ENW - VENI ( 016.Veni.192.188 to D.R.), and ERC under the European Union’s Horizon 2020 research and innovation programme ( 804089 ; ReCoDe to F.J.M.) and partially supported by the NWO Gravitation program BRAINSCAPES: Roadmap from Neurogenetics to Neurobiology ( NWO : 024.004.012 ) and Stichting Parkinson Fonds (to R.J.P.). Funding Information: We thank Dinos Meletis for input on our manuscript; Eric Turner for Brn3a-tauLacZ mice; and Kiochi Hashikawa, Garret Stuber, Michael Wallace, Bernardo Sabatini, Shristi Pandey, and Alexander Schier for sharing data. This research was supported by the Netherlands Organisation for Scientific Research (ALW-VICI 865.14.004 to R.J.P.), ENW-VENI (016.Veni.192.188 to D.R.), and ERC under the European Union's Horizon 2020 research and innovation programme (804089; ReCoDe to F.J.M.) and partially supported by the NWO Gravitation program BRAINSCAPES: Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012) and Stichting Parkinson Fonds (to R.J.P.). L.L.v.d.H. and R.J.P. designed the study and wrote the manuscript with help from all authors. L.L.v.d.H. D.R. and O.G. designed and performed experiments with help from J.E.B. T.E.S. R.E.v.D. Y.A. C.V.D.M. and N.C.H.v.K.; and M.H.B. D.P. and K.W. helped with performing MAGMA analysis. F.J.M. and O.B. designed experiments and aided in data analysis. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. Publisher Copyright: © 2022 The Author(s)
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