IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-52443-x.html
   My bibliography  Save this article

Conserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion

Author

Listed:
  • Soraia Barão

    (Johns Hopkins University School of Medicine)

  • Yijun Xu

    (Johns Hopkins University School of Medicine)

  • José P. Llongueras

    (Johns Hopkins University School of Medicine)

  • Rachel Vistein

    (Johns Hopkins University School of Medicine)

  • Loyal Goff

    (Johns Hopkins University School of Medicine)

  • Kristina J. Nielsen

    (Johns Hopkins University School of Medicine)

  • Byoung-Il Bae

    (University of Connecticut School of Medicine)

  • Richard S. Smith

    (Department of Pharmacology)

  • Christopher A. Walsh

    (Harvard Medical School
    Harvard Medical School)

  • Genevieve Stein-O’Brien

    (Johns Hopkins University School of Medicine)

  • Ulrich Müller

    (Johns Hopkins University School of Medicine)

Abstract

The neocortex varies in size and complexity among mammals due to the tremendous variability in the number and diversity of neuronal subtypes across species. The increased cellular diversity is paralleled by the expansion of the pool of neocortical progenitors and the emergence of indirect neurogenesis during brain evolution. The molecular pathways that control these biological processes and are disrupted in neurological disorders remain largely unknown. Here we show that the transcription factors BRN1 and BRN2 have an evolutionary conserved function in neocortical progenitors to control their proliferative capacity and the switch from direct to indirect neurogenesis. Functional studies in mice and ferrets show that BRN1/2 act in concert with NOTCH and primary microcephaly genes to regulate progenitor behavior. Analysis of transcriptomics data from genetically modified macaques provides evidence that these molecular pathways are conserved in non-human primates. Our findings thus demonstrate that BRN1/2 are central regulators of gene expression programs in neocortical progenitors critical to determine brain size during evolution.

Suggested Citation

  • Soraia Barão & Yijun Xu & José P. Llongueras & Rachel Vistein & Loyal Goff & Kristina J. Nielsen & Byoung-Il Bae & Richard S. Smith & Christopher A. Walsh & Genevieve Stein-O’Brien & Ulrich Müller, 2024. "Conserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52443-x
    DOI: 10.1038/s41467-024-52443-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-52443-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-52443-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Daniela J. Di Bella & Ehsan Habibi & Robert R. Stickels & Gabriele Scalia & Juliana Brown & Payman Yadollahpour & Sung Min Yang & Catherine Abbate & Tommaso Biancalani & Evan Z. Macosko & Fei Chen & A, 2021. "Molecular logic of cellular diversification in the mouse cerebral cortex," Nature, Nature, vol. 595(7868), pages 554-559, July.
    2. David V. Hansen & Jan H. Lui & Philip R. L. Parker & Arnold R. Kriegstein, 2010. "Neurogenic radial glia in the outer subventricular zone of human neocortex," Nature, Nature, vol. 464(7288), pages 554-561, March.
    3. Junyue Cao & Malte Spielmann & Xiaojie Qiu & Xingfan Huang & Daniel M. Ibrahim & Andrew J. Hill & Fan Zhang & Stefan Mundlos & Lena Christiansen & Frank J. Steemers & Cole Trapnell & Jay Shendure, 2019. "The single-cell transcriptional landscape of mammalian organogenesis," Nature, Nature, vol. 566(7745), pages 496-502, February.
    4. Eric H. Schroeter & Jeffrey A. Kisslinger & Raphael Kopan, 1998. "Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain," Nature, Nature, vol. 393(6683), pages 382-386, May.
    5. Daniela J. Di Bella & Ehsan Habibi & Robert R. Stickels & Gabriele Scalia & Juliana Brown & Payman Yadollahpour & Sung Min Yang & Catherine Abbate & Tommaso Biancalani & Evan Z. Macosko & Fei Chen & A, 2021. "Author Correction: Molecular logic of cellular diversification in the mouse cerebral cortex," Nature, Nature, vol. 596(7873), pages 11-11, August.
    6. Stephen C. Noctor & Alexander C. Flint & Tamily A. Weissman & Ryan S. Dammerman & Arnold R. Kriegstein, 2001. "Neurons derived from radial glial cells establish radial units in neocortex," Nature, Nature, vol. 409(6821), pages 714-720, February.
    7. Matthew B. Johnson & Xingshen Sun & Andrew Kodani & Rebeca Borges-Monroy & Kelly M. Girskis & Steven C. Ryu & Peter P. Wang & Komal Patel & Dilenny M. Gonzalez & Yu Mi Woo & Ziying Yan & Bo Liang & Ri, 2018. "Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size," Nature, Nature, vol. 556(7701), pages 370-375, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xiangling Feng & Yingjie Gao & Fan Chu & Yuwen Shan & Meicheng Liu & Yaoyi Wang & Ying Zhu & Qing Lu & Mingfeng Li, 2025. "Cortical arealization of interneurons defines shared and distinct molecular programs in developing human and macaque brains," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    2. Allen Yen & Simona Sarafinovska & Xuhua Chen & Dominic D. Skinner & Fatjon Leti & MariaLynn Crosby & Jessica Hoisington-Lopez & Yizhe Wu & Jiayang Chen & Zipeng A. Li & Kevin K. Noguchi & Robi D. Mitr, 2024. "MYT1L deficiency impairs excitatory neuron trajectory during cortical development," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Qingnan Liang & Yuefan Huang & Shan He & Ken Chen, 2023. "Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Allen W. Lynch & Myles Brown & Clifford A. Meyer, 2023. "Multi-batch single-cell comparative atlas construction by deep learning disentanglement," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    5. Chowon Kim & Nayeon Kang & Sunhong Min & Ramar Thangam & Sungkyu Lee & Hyunsik Hong & Kanghyeon Kim & Seong Yeol Kim & Dahee Kim & Hyunji Rha & Kyong-Ryol Tag & Hyun-Jeong Lee & Nem Singh & Daun Jeong, 2024. "Modularity-based mathematical modeling of ligand inter-nanocluster connectivity for unraveling reversible stem cell regulation," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    6. Jia-Ru Wei & Zhao-Zhe Hao & Chuan Xu & Mengyao Huang & Lei Tang & Nana Xu & Ruifeng Liu & Yuhui Shen & Sarah A. Teichmann & Zhichao Miao & Sheng Liu, 2022. "Identification of visual cortex cell types and species differences using single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    7. Abhijit Chakraborty & Jeffrey G. Wang & Ferhat Ay, 2022. "dcHiC detects differential compartments across multiple Hi-C datasets," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    8. Zeinab Asgarian & Marcio Guiomar Oliveira & Agata Stryjewska & Ioannis Maragkos & Anna Noren Rubin & Lorenza Magno & Vassilis Pachnis & Mohammadmersad Ghorbani & Scott Wayne Hiebert & Myrto Denaxa & N, 2022. "MTG8 interacts with LHX6 to specify cortical interneuron subtype identity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. Dafina M. Angelova & Aleksandra Tsolova & Malwina Prater & Noura Ballasy & Wendi Bacon & Russell S. Hamilton & Danielle Blackwell & Ziyi Yu & Xin Li & Xin Liu & Myriam Hemberger & D. Stephen Charnock-, 2025. "Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    10. J. McClatchy & R. Strogantsev & E. Wolfe & H. Y. Lin & M. Mohammadhosseini & B. A. Davis & C. Eden & D. Goldman & W. H. Fleming & P. Conley & G. Wu & L. Cimmino & H. Mohammed & A. Agarwal, 2023. "Clonal hematopoiesis related TET2 loss-of-function impedes IL1β-mediated epigenetic reprogramming in hematopoietic stem and progenitor cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Ci Fu & Xiang Zhang & Amanda O. Veri & Kali R. Iyer & Emma Lash & Alice Xue & Huijuan Yan & Nicole M. Revie & Cassandra Wong & Zhen-Yuan Lin & Elizabeth J. Polvi & Sean D. Liston & Benjamin VanderSlui, 2021. "Leveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    12. Sandra Curras-Alonso & Juliette Soulier & Thomas Defard & Christian Weber & Sophie Heinrich & Hugo Laporte & Sophie Leboucher & Sonia Lameiras & Marie Dutreix & Vincent Favaudon & Florian Massip & Tho, 2023. "An interactive murine single-cell atlas of the lung responses to radiation injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    13. Seung-Hyun Jung & Byung-Hee Hwang & Sun Shin & Eun-Hye Park & Sin-Hee Park & Chan Woo Kim & Eunmin Kim & Eunho Choo & Ik Jun Choi & Filip K. Swirski & Kiyuk Chang & Yeun-Jun Chung, 2022. "Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2hi macrophages in infarcted hearts," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Zhijie Liao & Kuldeep Kumar & Jakub Kopal & Guillaume Huguet & Zohra Saci & Martineau Jean-Louis & Zdenka Pausova & Igor Jurisica & Carrie E. Bearden & Sebastien Jacquemont & Tomas Paus, 2025. "Copy number variants and the tangential expansion of the cerebral cortex," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    15. Hailun Zhu & Sihai Dave Zhao & Alokananda Ray & Yu Zhang & Xin Li, 2022. "A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    16. Luke Simpson & Andrew Strange & Doris Klisch & Sophie Kraunsoe & Takuya Azami & Daniel Goszczynski & Triet Minh & Benjamin Planells & Nadine Holmes & Fei Sang & Sonal Henson & Matthew Loose & Jennifer, 2024. "A single-cell atlas of pig gastrulation as a resource for comparative embryology," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    17. Umji Lee & Yadong Zhang & Yonglin Zhu & Allen Chilun Luo & Liyan Gong & Daniel M. Tremmel & Yunhye Kim & Victoria Sofia Villarreal & Xi Wang & Ruei-Zeng Lin & Miao Cui & Minglin Ma & Ke Yuan & Kai Wan, 2024. "Robust differentiation of human pluripotent stem cells into mural progenitor cells via transient activation of NKX3.1," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    18. Andrea Flesken-Nikitin & Coulter Q. Ralston & Dah-Jiun Fu & Andrea J. Micheli & Daryl J. Phuong & Blaine A. Harlan & Christopher S. Ashe & Amanda P. Armstrong & David W. McKellar & Sangeeta Ghuwalewal, 2024. "Pre-ciliated tubal epithelial cells are prone to initiation of high-grade serous ovarian carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    19. Dan Frumkin & Adam Wasserstrom & Shai Kaplan & Uriel Feige & Ehud Shapiro, 2005. "Genomic Variability within an Organism Exposes Its Cell Lineage Tree," PLOS Computational Biology, Public Library of Science, vol. 1(5), pages 1-13, October.
    20. Yuma Takano & Jun Suzuki & Kotaro Nomura & Gento Fujii & Junko Zenkoh & Hitomi Kawai & Yuta Kuze & Yukie Kashima & Satoi Nagasawa & Yuka Nakamura & Motohiro Kojima & Katsuya Tsuchihara & Masahide Seki, 2024. "Spatially resolved gene expression profiling of tumor microenvironment reveals key steps of lung adenocarcinoma development," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52443-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.