Molecular programs guiding arealization of descending cortical pathways

Article Article scientifique Article Molecular programs guiding arealization of descending cortical pathways eng 2024-09-11 2024-10 author Abe Philipp 0000-0002-8067-1802 Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.,Institute of Anatomy, Medical Faculty Carl Gustav Carus, Technische Universität Dresden School of Medicine, Dresden, Germany. 889742 author Lavalley Adrien Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.,Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland. 697244 author Morassut Ilaria 0000-0001-9735-9308 Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. 966598 Département de neurosciences fondamentales (NEUFO) author Santinha Antonio J 0000-0002-1171-3802 Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. author Roig Puiggros Sergi 0000-0001-5909-218X Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. 931871 Département de neurosciences fondamentales (NEUFO) author Javed Awais Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. 966110 Département de neurosciences fondamentales (NEUFO) author Klingler Esther Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.,VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium. 831648 author Baumann Natalia 0000-0003-4518-2103 Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. 752648 Département de neurosciences fondamentales (NEUFO) author Prados Julien 0000-0002-8546-241X Bioinformatic Support Platform, University of Geneva, Geneva, Switzerland. 561771 Services communs de la faculté de médecine (SCMU) author Platt Randall J 0000-0002-2914-7052 Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.,Basel Research Center for Child Health, Basel, Switzerland.,Department of Chemistry, University of Basel, Basel, Switzerland.,NCCR Molecular Systems Engineering, Basel, Switzerland. author Jabaudon Denis 0000-0003-2438-4769 Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland. denis.jabaudon@unige.ch.,Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland. denis.jabaudon@unige.ch.,Université Paris Cité, Imagine Institute, Paris, France. denis.jabaudon@unige.ch. 682473 Département de neurosciences fondamentales (NEUFO) 644-651 10.1038/s41586-024-07895-y 39261725 0028-0836 https://www.nature.com/articles/s41586-024-07895-y Layer 5 extratelencephalic (ET) neurons are present across neocortical areas and send axons to multiple subcortical targets1-6. Two cardinal subtypes exist7,8: (1) Slco2a1-expressing neurons (ETdist), which predominate in the motor cortex and project distally to the pons, medulla and spinal cord; and (2) Nprs1- or Hpgd-expressing neurons (ETprox), which predominate in the visual cortex and project more proximally to the pons and thalamus. An understanding of how area-specific ETdist and ETprox emerge during development is important because they are critical for fine motor skills and are susceptible to spinal cord injury and amyotrophic lateral sclerosis9-12. Here, using cross-areal mapping of axonal projections in the mouse neocortex, we identify the subtype-specific developmental dynamics of ET neurons. Whereas subsets of ETprox emerge by pruning of ETdist axons, others emerge de novo. We outline corresponding subtype-specific developmental transcriptional programs using single-nucleus sequencing. Leveraging these findings, we use postnatal in vivo knockdown of subtype-specific transcription factors to reprogram ET neuron connectivity towards more proximal targets. Together, these results show the functional transcriptional programs driving ET neuron diversity and uncover cell subtype-specific gene regulatory networks that can be manipulated to direct target specificity in motor corticofugal pathways. Animals Axons / metabolism Female Gene Expression Regulation, Developmental Male Mice Motor Cortex / cytology Motor Cortex / metabolism Neocortex / anatomy & histology Neocortex / cytology Neocortex / metabolism Neural Pathways Neurons / cytology Neurons / metabolism Single-Cell Gene Expression Analysis Transcription Factors / metabolism Dewey 616.8 Swiss National Science Foundation Identification of convergent molecular pathways in autism spectrum disorder by in utero genome editing and transcriptional profiling of cortical projection neuron subtypes 175830 CH Projects Swiss National Science Foundation Dynamic consortium interactions that establish the microbiota during weaning 205965 CH Programmes Swiss National Science Foundation Engineering safety of live microbials for human health 211573 CH Programmes Swiss National Science Foundation NCCR MSE: Molecular Systems Engineering (phase II) 182895 CH Programmes European Commission Reconstructing cellular histories with transcriptional recording 851021 CRISPRhistory EU H2020 53 Département de neurosciences fondamentales 21A 61 Département des neurosciences cliniques 226 false 540 Neurobiologie développementale et plasticité 880 48a82112-9f30-4dde-a32a-47c02fceac29 Bioinformatics Support Platform 0a6434c9-7972-44ea-8708-82e501660dc7 Biomedical Data Science Facility 0a6434c9-7972-44ea-8708-82e501660dc7 Biomedical Data Science Facility https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE270951 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE271067 https://genebrowser.unige.ch/L5ETdev/ https://portal.brain-map.org/atlases-and-data/rnaseq/mouse-v1-and-alm-smart-seq https://portal.brain-map.org/atlases-and-data/rnaseq/mouse-whole-cortex-and-hippocampus-10x https://assets.nemoarchive.org/dat-15ao5au https://github.com/abe-neuro/L5ET-DEV https://github.com/awaisj14/CellOracle_ET https://github.com/pradosj/docker_sindbis Nature 634 8034 c939f463-3e5e-4cfe-979a-9ddd998b3085 Article (Published version) Restricted Article_scientifique_from_crossref.pdf 53691409 application/pdf 575fc5e76bb463fd7eb875552a5c775e4bb6ba04d80af839a2122373088381e7 10349cb5-dbfa-41b3-8768-11f2a22d0cff Supplemental data Restricted 41586_2024_7895_MOESM1_ESM.pdf 684172 application/pdf 9eece0a61d728a8c5aee6dfc1c97bba08b48d5532b44967431eb17823f457d5c e7630834-b7ef-4e9e-9f0c-09e939387570 Supplemental data Restricted 41586_2024_7895_MOESM3_ESM.zip 2195643 application/zip 411ca8619b397340b35ad66adb54bd12bc7ff88cb90ab97abac6070bfce9201c restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques

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Molecular programs guiding arealization of descending cortical pathways	Nature	2024	114	0
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