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PCM1 coordinates centrosome asymmetry with polarized endosome dynamics to regulate daughter cell fate

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  • Xiang Zhao

    (San Francisco, Department of Bioengineering and Therapeutic Sciences, Pharmaceutical Chemistry, Programs in Biological Sciences and Quantitative Biosciences, Institute of Human Genetics, Kavli Institute for Fundamental Neuroscience, Bakar Aging Research Institute, University of California
    San Francisco, Chan Zuckerberg Biohub)

  • Vincent Mouilleau

    (San Francisco, Department of Bioengineering and Therapeutic Sciences, Pharmaceutical Chemistry, Programs in Biological Sciences and Quantitative Biosciences, Institute of Human Genetics, Kavli Institute for Fundamental Neuroscience, Bakar Aging Research Institute, University of California)

  • Yiqi Wang

    (Huazhong Agricultural University, College of Biomedicine and Health, College of Life Science and Technology)

  • Ahmet Can Solak

    (San Francisco, Chan Zuckerberg Biohub
    Lawrence Livermore National Laboratory)

  • Jason Q. Garcia

    (San Francisco, Department of Bioengineering and Therapeutic Sciences, Pharmaceutical Chemistry, Programs in Biological Sciences and Quantitative Biosciences, Institute of Human Genetics, Kavli Institute for Fundamental Neuroscience, Bakar Aging Research Institute, University of California)

  • Xinye Chen

    (San Francisco, Department of Bioengineering and Therapeutic Sciences, Pharmaceutical Chemistry, Programs in Biological Sciences and Quantitative Biosciences, Institute of Human Genetics, Kavli Institute for Fundamental Neuroscience, Bakar Aging Research Institute, University of California
    Tsinghua University, Department of Automation)

  • Xiaoyu Shi

    (Irvine, Department of Biomedical Engineering, Developmental and Cell Biology, Chemistry, University of California)

  • Christopher J. Wilkinson

    (Egham, Centre for Biomedical Sciences, Department of Biological Sciences, Royal Holloway University of London)

  • Loïc A. Royer

    (San Francisco, Chan Zuckerberg Biohub)

  • Zhiqiang Dong

    (San Francisco, Department of Bioengineering and Therapeutic Sciences, Pharmaceutical Chemistry, Programs in Biological Sciences and Quantitative Biosciences, Institute of Human Genetics, Kavli Institute for Fundamental Neuroscience, Bakar Aging Research Institute, University of California
    Huazhong Agricultural University, College of Biomedicine and Health, College of Life Science and Technology)

  • Su Guo

    (San Francisco, Department of Bioengineering and Therapeutic Sciences, Pharmaceutical Chemistry, Programs in Biological Sciences and Quantitative Biosciences, Institute of Human Genetics, Kavli Institute for Fundamental Neuroscience, Bakar Aging Research Institute, University of California)

Abstract

Vertebrate radial glia progenitors (RGPs) balance self-renewal and differentiation through asymmetric cell division (ACD), which involves unequal centrosome inheritance. How centrosome asymmetry directs cell fate remains poorly understood. Here, we identify Pericentriolar material 1 (Pcm1) as a key player in this process. In zebrafish embryonic RGPs, Pcm1 is asymmetrically associated with Cep83, a mother centrosome marker. Using in vivo time-lapse imaging and nanoscale-resolution expansion microscopy, we detect Pcm1 on Notch ligand-containing endosomes, where it interacts–either directly or indirectly–with Par-3 and dynein. Loss of pcm1 disrupts endosome dynamics, increasing neuronal differentiation at the expense of RGP self-renewal. Mechanistically, Pcm1 facilitates the transition from Rab5b to Rab11a and promotes the assembly of Par-3 and dynein macromolecular complexes on recycling endosomes. Furthermore, we find conserved PARD3-PCM1-CEP83-RAB11 associations in human cortical brain organoids. Our findings uncover that Pcm1 links centrosome asymmetry to polarized endosome trafficking, thereby regulating RGP fate decisions.

Suggested Citation

  • Xiang Zhao & Vincent Mouilleau & Yiqi Wang & Ahmet Can Solak & Jason Q. Garcia & Xinye Chen & Xiaoyu Shi & Christopher J. Wilkinson & Loïc A. Royer & Zhiqiang Dong & Su Guo, 2025. "PCM1 coordinates centrosome asymmetry with polarized endosome dynamics to regulate daughter cell fate," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65756-2
    DOI: 10.1038/s41467-025-65756-2
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