Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex
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 co...
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| Formaat: | Artigo |
| Taal: | Engels |
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2023
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| Online toegang: | https://doi.org/10.1038/s41467-023-41730-8 https://www.nature.com/articles/s41467-023-41730-8.pdf |
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| _version_ | 1838739256004050944 |
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| access_facet | Acesso Aberto |
| author | Iva Salamon Yongkyu Park Terezija Miškić Janja Kopić Paul G. Matteson Nicholas F. Page Alfonso Roque Geoffrey McAuliffe John Favate Marta Garcia‐Forn Premal Shah Miloš Judáš James H. Millonig Ivica Kostović Silvia De Rubeis Ronald P. Hart Željka Krsnik Mladen‐Roko Rašin |
| author_facet | Iva Salamon Yongkyu Park Terezija Miškić Janja Kopić Paul G. Matteson Nicholas F. Page Alfonso Roque Geoffrey McAuliffe John Favate Marta Garcia‐Forn Premal Shah Miloš Judáš James H. Millonig Ivica Kostović Silvia De Rubeis Ronald P. Hart Željka Krsnik Mladen‐Roko Rašin |
| cited_by_count_is | 23 |
| collection | OpenAlex |
| description | 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. |
| format | Artigo |
| frbr_group_id_str | doi-10.1038/s41467-023-41730-8 |
| id | openalex-W4387079730 |
| institution | Johnson University |
| issn_str | 2041-1723 |
| issue_str | 1 |
| journal_title_str | Nature Communications |
| language | eng |
| publishDate | 2023 |
| publisher_str | Nature Portfolio |
| spellingShingle | Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex Iva Salamon Yongkyu Park Terezija Miškić Janja Kopić Paul G. Matteson Nicholas F. Page Alfonso Roque Geoffrey McAuliffe John Favate Marta Garcia‐Forn Premal Shah Miloš Judáš James H. Millonig Ivica Kostović Silvia De Rubeis Ronald P. Hart Željka Krsnik Mladen‐Roko Rašin |
| title | Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex |
| title_full | Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex |
| title_fullStr | Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex |
| title_full_unstemmed | Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex |
| title_short | Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex |
| topic_facet | Subplate Neocortex Synaptogenesis Biology Forebrain Translation (biology) Neuroscience RNA-binding protein Polysome Synapse RNA Messenger RNA Cell biology Cerebral cortex Gene Genetics Central nervous system Ribosome |
| url | https://doi.org/10.1038/s41467-023-41730-8 https://www.nature.com/articles/s41467-023-41730-8.pdf |
| volume_str | 14 |