Nova proteins direct synaptic integration of somatostatin interneurons through activity-dependent alternative splicing.

Autor:	Ibrahim LA; Department of Neurobiology, Harvard Medical School, Boston, United States.; Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.; Stanley Center at the Broad, Cambridge, United States., Wamsley B; NYU Neuroscience Institute and the Department of Neuroscience and Physiology, Smilow Research Center, New York University School of Medicine, New York, United States., Alghamdi N; Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia., Yusuf N; Department of Neurobiology, Harvard Medical School, Boston, United States.; Stanley Center at the Broad, Cambridge, United States.; NYU Neuroscience Institute and the Department of Neuroscience and Physiology, Smilow Research Center, New York University School of Medicine, New York, United States., Sevier E; Department of Neurobiology, Harvard Medical School, Boston, United States.; Stanley Center at the Broad, Cambridge, United States., Hairston A; Department of Neurobiology, Harvard Medical School, Boston, United States., Sherer M; Department of Neurobiology, Harvard Medical School, Boston, United States.; Stanley Center at the Broad, Cambridge, United States., Jaglin XH; NYU Neuroscience Institute and the Department of Neuroscience and Physiology, Smilow Research Center, New York University School of Medicine, New York, United States., Xu Q; Center for Genomics & Systems Biology, New York University, Abu Dhabi, United Arab Emirates., Guo L; Center for Genomics & Systems Biology, New York University, Abu Dhabi, United Arab Emirates., Khodadadi-Jamayran A; Genome Technology Center, Applied Bioinformatics Laboratories, NYU Langone Medical Center, New York, United States., Favuzzi E; Department of Neurobiology, Harvard Medical School, Boston, United States.; Stanley Center at the Broad, Cambridge, United States., Yuan Y; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, United States., Dimidschstein J; Stanley Center at the Broad, Cambridge, United States., Darnell RB; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, United States., Fishell G; Department of Neurobiology, Harvard Medical School, Boston, United States.; Stanley Center at the Broad, Cambridge, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Jun 22; Vol. 12. Date of Electronic Publication: 2023 Jun 22.
DOI:	10.7554/eLife.86842
Abstrakt:	Somatostatin interneurons are the earliest born population of cortical inhibitory cells. They are crucial to support normal brain development and function; however, the mechanisms underlying their integration into nascent cortical circuitry are not well understood. In this study, we begin by demonstrating that the maturation of somatostatin interneurons in mouse somatosensory cortex is activity dependent. We then investigated the relationship between activity, alternative splicing, and synapse formation within this population. Specifically, we discovered that the Nova family of RNA-binding proteins are activity-dependent and are essential for the maturation of somatostatin interneurons, as well as their afferent and efferent connectivity. Within this population, Nova2 preferentially mediates the alternative splicing of genes required for axonal formation and synaptic function independently from its effect on gene expression. Hence, our work demonstrates that the Nova family of proteins through alternative splicing are centrally involved in coupling developmental neuronal activity to cortical circuit formation. Competing Interests: LI, BW, NA, NY, ES, AH, MS, XJ, QX, LG, AJ, EF, YY, RD No competing interests declared, JD, GF Founder of Regal Therapeutics (© 2023, Ibrahim, Wamsley et al.)
Databáze:	MEDLINE
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