Rbfox1 Mediates Cell-type-Specific Splicing in Cortical Interneurons

Brie Wamsley; Xavier Hubert Jaglin; Emilia Favuzzi; Giulia Quattrocolo; Maximiliano José Nigro; Nusrath Yusuf; Alireza Khodadadi-Jamayran; Bernardo Rudy; Gord Fishell

doi:10.1016/j.neuron.2018.09.026

Rbfox1 Mediates Cell-type-Specific Splicing in Cortical Interneurons

Neuron. 2018 Nov 21;100(4):846-859.e7. doi: 10.1016/j.neuron.2018.09.026. Epub 2018 Oct 11.

Authors

Brie Wamsley¹, Xavier Hubert Jaglin¹, Emilia Favuzzi², Giulia Quattrocolo³, Maximiliano José Nigro³, Nusrath Yusuf⁴, Alireza Khodadadi-Jamayran⁵, Bernardo Rudy³, Gord Fishell⁶

Affiliations

¹ NYU Neuroscience Institute and the Department of Neuroscience and Physiology, Smilow Research Center, New York University School of Medicine, 522 First Avenue, New York, NY 10016, USA; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
² Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Stanley Center at the Broad, 75 Ames Street, Cambridge, MA 02142, USA.
³ NYU Neuroscience Institute and the Department of Neuroscience and Physiology, Smilow Research Center, New York University School of Medicine, 522 First Avenue, New York, NY 10016, USA.
⁴ NYU Neuroscience Institute and the Department of Neuroscience and Physiology, Smilow Research Center, New York University School of Medicine, 522 First Avenue, New York, NY 10016, USA; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Stanley Center at the Broad, 75 Ames Street, Cambridge, MA 02142, USA.
⁵ Genome Technology Center, Applied Bioinformatics Laboratories, NYU Langone Medical Center, 550 First Avenue, MSB 304, New York, NY 10016, USA.
⁶ NYU Neuroscience Institute and the Department of Neuroscience and Physiology, Smilow Research Center, New York University School of Medicine, 522 First Avenue, New York, NY 10016, USA; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Stanley Center at the Broad, 75 Ames Street, Cambridge, MA 02142, USA. Electronic address: gordon_fishell@hms.harvard.edu.

Abstract

Cortical interneurons display a remarkable diversity in their morphology, physiological properties, and connectivity. Elucidating the molecular determinants underlying this heterogeneity is essential for understanding interneuron development and function. We discovered that alternative splicing differentially regulates the integration of somatostatin- and parvalbumin-expressing interneurons into nascent cortical circuits through the cell-type-specific tailoring of mRNAs. Specifically, we identified a role for the activity-dependent splicing regulator Rbfox1 in the development of cortical interneuron-subtype-specific efferent connectivity. Our work demonstrates that Rbfox1 mediates largely non-overlapping alternative splicing programs within two distinct but related classes of interneurons.

Keywords: ASD; Rbfox1; alternative splicing; connectivity; interneuron; neurodevelopment; synapse.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Alternative Splicing / physiology*
Animals
Cerebral Cortex / cytology
Cerebral Cortex / physiology*
Interneurons / cytology
Interneurons / physiology*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Organ Culture Techniques
RNA Splicing Factors / physiology*

Substances

RNA Splicing Factors
Rbfox1 protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding