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

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  • 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
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    References listed on IDEAS

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    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. 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.
    5. 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.
    6. 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.
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