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

Leena Ali Ibrahim | Brie Wamsley | Norah Alghamdi | Nusrath Yusuf | Elaine Sevier | Ariel Hairston | Mia Sherer | Xavier Hubert Jaglin | Qing Xu | Lihua Guo | Alireza Khodadadi-Jamayran | Emilia Favuzzi | Yuan Yuan | Jordane Dimidschstein | Robert B Darnell | Gordon Fishell
eLife | 2023

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.

Pubmed ID: 37347149

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: P01 NS074972
  • Agency: NCI NIH HHS, United States
    Id: P30 CA016087
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH071679
  • Agency: NINDS NIH HHS, United States
    Id: R35 NS097404
  • Agency: NIH HHS, United States
    Id: UG3 MH120096
  • Agency: NIH HHS, United States
    Id: R01 NS081297
  • Agency: NIMH NIH HHS, United States
    Id: UG3 MH120096
  • Agency: NIH HHS, United States
    Id: R01 MH071679
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS081297
  • Agency: NIH HHS, United States
    Id: P01 NS074972
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR000038

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