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Lgl1 controls NG2 endocytic pathway to regulate oligodendrocyte differentiation and asymmetric cell division and gliomagenesis

Author

Listed:
  • Mathieu Daynac

    (University of California San Francisco)

  • Malek Chouchane

    (University of California San Francisco)

  • Hannah Y. Collins

    (University of California San Francisco
    Stanford University)

  • Nicole E. Murphy

    (University of California San Francisco)

  • Noemi Andor

    (University of California San Francisco
    Stanford University)

  • Jianqin Niu

    (University of California San Francisco)

  • Stephen P. J. Fancy

    (University of California San Francisco
    University of California San Francisco)

  • William B. Stallcup

    (Sanford Burnham Prebys Medical Discovery Institute)

  • Claudia K. Petritsch

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

Abstract

Oligodendrocyte progenitor cells (OPC) undergo asymmetric cell division (ACD) to generate one OPC and one differentiating oligodendrocyte (OL) progeny. Loss of pro-mitotic proteoglycan and OPC marker NG2 in the OL progeny is the earliest immunophenotypic change of unknown mechanism that indicates differentiation commitment. Here, we report that expression of the mouse homolog of Drosophila tumor suppressor Lethal giant larvae 1 (Lgl1) is induced during OL differentiation. Lgl1 conditional knockout OPC progeny retain NG2 and show reduced OL differentiation, while undergoing more symmetric self-renewing divisions at the expense of asymmetric divisions. Moreover, Lgl1 and hemizygous Ink4a/Arf knockouts in OPC synergistically induce gliomagenesis. Time lapse and total internal reflection microscopy reveals a critical role for Lgl1 in NG2 endocytic routing and links aberrant NG2 recycling to failed differentiation. These data establish Lgl1 as a suppressor of gliomagenesis and positive regulator of asymmetric division and differentiation in the healthy and demyelinated murine brain.

Suggested Citation

  • Mathieu Daynac & Malek Chouchane & Hannah Y. Collins & Nicole E. Murphy & Noemi Andor & Jianqin Niu & Stephen P. J. Fancy & William B. Stallcup & Claudia K. Petritsch, 2018. "Lgl1 controls NG2 endocytic pathway to regulate oligodendrocyte differentiation and asymmetric cell division and gliomagenesis," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05099-3
    DOI: 10.1038/s41467-018-05099-3
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