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. 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.
    2. 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.
    3. 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.
    4. 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.
    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. "Molecular logic of cellular diversification in the mouse cerebral cortex," Nature, Nature, vol. 595(7868), pages 554-559, July.
    6. 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.
    7. 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.
    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. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. Sivakamasundari Vijayakumar & Roberta Sala & Gugene Kang & Angela Chen & Michelle Ann Pablo & Abidemi Ismail Adebayo & Andrea Cipriano & Jonas L. Fowler & Danielle L. Gomes & Lay Teng Ang & Kyle M. Lo, 2023. "Monolayer platform to generate and purify primordial germ-like cells in vitro provides insights into human germline specification," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    7. Brian DeVeale & Leqian Liu & Ryan Boileau & Jennifer Swindlehurst-Chan & Bryan Marsh & Jacob W. Freimer & Adam Abate & Robert Blelloch, 2022. "G1/S restriction point coordinates phasic gene expression and cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Yasuaki Uehara & Yusuke Tanaka & Shuyang Zhao & Nikolaos M. Nikolaidis & Lori B. Pitstick & Huixing Wu & Jane J. Yu & Erik Zhang & Yoshihiro Hasegawa & John G. Noel & Jason C. Gardner & Elizabeth J. K, 2023. "Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    9. 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.
    10. 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.
    11. Junyi Chen & Xiaoying Wang & Anjun Ma & Qi-En Wang & Bingqiang Liu & Lang Li & Dong Xu & Qin Ma, 2022. "Deep transfer learning of cancer drug responses by integrating bulk and single-cell RNA-seq data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    12. Kotaro Shimizu & Junichi Kikuta & Yumi Ohta & Yutaka Uchida & Yu Miyamoto & Akito Morimoto & Shinya Yari & Takashi Sato & Takefumi Kamakura & Kazuo Oshima & Ryusuke Imai & Yu-Chen Liu & Daisuke Okuzak, 2023. "Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    13. Young Hee Lee & Yu-Been Kim & Kyu Sik Kim & Mirae Jang & Ha Young Song & Sang-Ho Jung & Dong-Soo Ha & Joon Seok Park & Jaegeon Lee & Kyung Min Kim & Deok-Hyeon Cheon & Inhyeok Baek & Min-Gi Shin & Eun, 2023. "Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    14. 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.
    15. 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.
    16. 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.
    17. 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.
    18. Hannah Drew Rickner & Lulu Jiang & Rui Hong & Nicholas K. O’Neill & Chromewell A. Mojica & Benjamin J. Snyder & Lushuang Zhang & Dipan Shaw & Maria Medalla & Benjamin Wolozin & Christine S. Cheng, 2022. "Single cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    19. Jingtao Wang & Gregory J. Fonseca & Jun Ding, 2024. "scSemiProfiler: Advancing large-scale single-cell studies through semi-profiling with deep generative models and active learning," Nature Communications, Nature, vol. 15(1), pages 1-27, December.
    20. 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.

    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.