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

First Author  Ibrahim LA Year  2023
Journal  Elife Volume  12
PubMed ID  37347149 Mgi Jnum  J:359186
Mgi Id  MGI:7785393 Doi  10.7554/eLife.86842
Citation  Ibrahim LA, et al. (2023) Nova proteins direct synaptic integration of somatostatin interneurons through activity-dependent alternative splicing. Elife 12
abstractText  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.
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