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

Autor: Salamon I; Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.; Rutgers University, School of Graduate Studies, New Brunswick, NJ, 08854, USA., Park Y; Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA., Miškić T; Croatian Institute for Brain Research, Center of Research Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, 10000, Croatia., Kopić J; Croatian Institute for Brain Research, Center of Research Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, 10000, Croatia., Matteson P; Center for Advanced Biotechnology and Medicine, Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA., Page NF; Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA., Roque A; Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA., McAuliffe GW; Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA., Favate J; Department of Genetics, Rutgers University, Piscataway, NJ, 08854, USA., Garcia-Forn M; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; The Alper Center for Neural Development and Regeneration, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Shah P; Department of Genetics, Rutgers University, Piscataway, NJ, 08854, USA., Judaš M; Croatian Institute for Brain Research, Center of Research Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, 10000, Croatia., Millonig JH; Center for Advanced Biotechnology and Medicine, Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA., Kostović I; Croatian Institute for Brain Research, Center of Research Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, 10000, Croatia., De Rubeis S; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; The Alper Center for Neural Development and Regeneration, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Hart RP; Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA., Krsnik Ž; Croatian Institute for Brain Research, Center of Research Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, 10000, Croatia. zeljka.krsnik@hiim.hr., Rasin MR; Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA. roko.rasin@rutgers.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Sep 27; Vol. 14 (1), pp. 6025. Date of Electronic Publication: 2023 Sep 27.
DOI: 10.1038/s41467-023-41730-8
Abstrakt: 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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