IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28636-7.html
   My bibliography  Save this article

The histone demethylase Kdm6b regulates subtype diversification of mouse spinal motor neurons during development

Author

Listed:
  • Wenxian Wang

    (University at Buffalo, The State University of New York (SUNY))

  • Hyeyoung Cho

    (Oregon Health & Science University)

  • Jae W. Lee

    (University at Buffalo, The State University of New York (SUNY))

  • Soo-Kyung Lee

    (University at Buffalo, The State University of New York (SUNY))

Abstract

How a single neuronal population diversifies into subtypes with distinct synaptic targets is a fundamental topic in neuroscience whose underlying mechanisms are unclear. Here, we show that the histone H3-lysine 27 demethylase Kdm6b regulates the diversification of motor neurons to distinct subtypes innervating different muscle targets during spinal cord development. In mouse embryonic motor neurons, Kdm6b promotes the medial motor column (MMC) and hypaxial motor column (HMC) fates while inhibiting the lateral motor column (LMC) and preganglionic motor column (PGC) identities. Our single-cell RNA-sequencing analyses reveal the heterogeneity of PGC, LMC, and MMC motor neurons. Further, our single-cell RNA-sequencing data, combined with mouse model studies, demonstrates that Kdm6b acquires cell fate specificity together with the transcription factor complex Isl1-Lhx3. Our study provides mechanistic insight into the gene regulatory network regulating neuronal cell-type diversification and defines a regulatory role of Kdm6b in the generation of motor neuron subtypes in the mouse spinal cord.

Suggested Citation

  • Wenxian Wang & Hyeyoung Cho & Jae W. Lee & Soo-Kyung Lee, 2022. "The histone demethylase Kdm6b regulates subtype diversification of mouse spinal motor neurons during development," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28636-7
    DOI: 10.1038/s41467-022-28636-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28636-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-28636-7?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. Karen P. Thiebes & Heejin Nam & Xiaolu A. Cambronne & Rongkun Shen & Stacey M. Glasgow & Hyong-Ho Cho & Ji-sun Kwon & Richard H. Goodman & Jae W. Lee & Seunghee Lee & Soo-Kyung Lee, 2015. "Correction: Corrigendum: miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3," Nature Communications, Nature, vol. 6(1), pages 1-1, November.
    2. Fei Lan & Peter E. Bayliss & John L. Rinn & Johnathan R. Whetstine & Jordon K. Wang & Shuzhen Chen & Shigeki Iwase & Roman Alpatov & Irina Issaeva & Eli Canaani & Thomas M. Roberts & Howard Y. Chang &, 2007. "A histone H3 lysine 27 demethylase regulates animal posterior development," Nature, Nature, vol. 449(7163), pages 689-694, October.
    3. Kristen Jepsen & Derek Solum & Tianyuan Zhou & Robert J. McEvilly & Hyun-Jung Kim & Christopher K. Glass & Ola Hermanson & Michael G. Rosenfeld, 2007. "SMRT-mediated repression of an H3K27 demethylase in progression from neural stem cell to neuron," Nature, Nature, vol. 450(7168), pages 415-419, November.
    4. Eric Dessaud & Lin Lin Yang & Katy Hill & Barny Cox & Fausto Ulloa & Ana Ribeiro & Anita Mynett & Bennett G. Novitch & James Briscoe, 2007. "Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism," Nature, Nature, vol. 450(7170), pages 717-720, November.
    5. Karen P. Thiebes & Heejin Nam & Xiaolu A. Cambronne & Rongkun Shen & Stacey M. Glasgow & Hyong-Ho Cho & Ji-sun Kwon & Richard H. Goodman & Jae W. Lee & Seunghee Lee & Soo-Kyung Lee, 2015. "miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    6. Kamal Sharma & Ann E. Leonard & Karen Lettieri & Samuel L. Pfaff, 2000. "Genetic and epigenetic mechanisms contribute to motor neuron pathfinding," Nature, Nature, vol. 406(6795), pages 515-519, August.
    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. Chakraborty, Priya & Jolly, Mohit Kumar & Roy, Ushasi & Ghosh, Sayantari, 2023. "Spatio-temporal pattern formation due to host-circuit interplay in gene expression dynamics," Chaos, Solitons & Fractals, Elsevier, vol. 167(C).
    2. Peter Langfelder & Fuying Gao & Nan Wang & David Howland & Seung Kwak & Thomas F Vogt & Jeffrey S Aaronson & Jim Rosinski & Giovanni Coppola & Steve Horvath & X William Yang, 2018. "MicroRNA signatures of endogenous Huntingtin CAG repeat expansion in mice," PLOS ONE, Public Library of Science, vol. 13(1), pages 1-20, January.
    3. Roman Vetter & Dagmar Iber, 2022. "Precision of morphogen gradients in neural tube development," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Alek G. Erickson & Alessia Motta & Maria Eleni Kastriti & Steven Edwards & Fanny Coulpier & Emy Théoulle & Aliia Murtazina & Irina Poverennaya & Daniel Wies & Jeremy Ganofsky & Giovanni Canu & Francoi, 2024. "Motor innervation directs the correct development of the mouse sympathetic nervous system," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Andreas Lackner & Michael Müller & Magdalena Gamperl & Delyana Stoeva & Olivia Langmann & Henrieta Papuchova & Elisabeth Roitinger & Gerhard Dürnberger & Richard Imre & Karl Mechtler & Paulina A. Lato, 2023. "The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    6. Seth Teague & Gillian Primavera & Bohan Chen & Zong-Yuan Liu & LiAng Yao & Emily Freeburne & Hina Khan & Kyoung Jo & Craig Johnson & Idse Heemskerk, 2024. "Time-integrated BMP signaling determines fate in a stem cell model for early human development," Nature Communications, Nature, vol. 15(1), pages 1-18, 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:13:y:2022:i:1:d:10.1038_s41467-022-28636-7. 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.