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Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex

Author

Listed:
  • Iva Salamon

    (Rutgers University, Robert Wood Johnson Medical School
    Rutgers University, School of Graduate Studies)

  • Yongkyu Park

    (Rutgers University, Robert Wood Johnson Medical School)

  • Terezija Miškić

    (University of Zagreb, School of Medicine)

  • Janja Kopić

    (University of Zagreb, School of Medicine)

  • Paul Matteson

    (Rutgers Robert Wood Johnson Medical School)

  • Nicholas F. Page

    (Rutgers University, Robert Wood Johnson Medical School)

  • Alfonso Roque

    (Rutgers University, Robert Wood Johnson Medical School)

  • Geoffrey W. McAuliffe

    (Rutgers University, Robert Wood Johnson Medical School)

  • John Favate

    (Rutgers University)

  • Marta Garcia-Forn

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Premal Shah

    (Rutgers University)

  • Miloš Judaš

    (University of Zagreb, School of Medicine)

  • James H. Millonig

    (Rutgers Robert Wood Johnson Medical School)

  • Ivica Kostović

    (University of Zagreb, School of Medicine)

  • Silvia Rubeis

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Ronald P. Hart

    (The State University of New Jersey)

  • Željka Krsnik

    (University of Zagreb, School of Medicine)

  • Mladen-Roko Rasin

    (Rutgers University, Robert Wood Johnson Medical School)

Abstract

Abnormalities in neocortical and synaptic development are linked to neurodevelopmental disorders. However, the molecular and cellular mechanisms governing initial synapse formation in the prenatal neocortex remain poorly understood. Using polysome profiling coupled with snRNAseq on human cortical samples at various fetal phases, we identify human mRNAs, including those encoding synaptic proteins, with finely controlled translation in distinct cell populations of developing frontal neocortices. Examination of murine and human neocortex reveals that the RNA binding protein and translational regulator, CELF4, is expressed in compartments enriched in initial synaptogenesis: the marginal zone and the subplate. We also find that Celf4/CELF4-target mRNAs are encoded by risk genes for adverse neurodevelopmental outcomes translating into synaptic proteins. Surprisingly, deleting Celf4 in the forebrain disrupts the balance of subplate synapses in a sex-specific fashion. This highlights the significance of RNA binding proteins and mRNA translation in evolutionarily advanced synaptic development, potentially contributing to sex differences.

Suggested Citation

  • Iva Salamon & Yongkyu Park & Terezija Miškić & Janja Kopić & Paul Matteson & Nicholas F. Page & Alfonso Roque & Geoffrey W. McAuliffe & John Favate & Marta Garcia-Forn & Premal Shah & Miloš Judaš & Ja, 2023. "Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41730-8
    DOI: 10.1038/s41467-023-41730-8
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