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Abstract Details

RBFOX1 Regulates Both Splicing and Transcriptional Networks in Human Neuronal Development
Child Neurology/Developmental Neurobiology
S15 - (-)
002
RNA splicing plays a critical role in the programming of neuronal differentiation and, consequently, normal human neurodevelopment, and its disruption may underlie neurodevelopmental and neuropsychiatric disorders. The RNA-binding protein, fox-1 homolog (RBFOX1; also termed A2BP1 or FOX1), is a neuron-specific splicing factor predicted to regulate neuronal splicing networks clinically implicated in neurodevelopmental disease, including autism spectrum disorder (ASD), but only a few targets have been experimentally identified.
We used RNA sequencing to identify the RBFOX1 splicing network at a genome-wide level in primary human neural stem cells during differentiation.
We observe that RBFOX1 regulates a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors and synaptic proteins. Downstream alterations in gene expression define an additional transcriptional network regulated by RBFOX1 involved in neurodevelopmental pathways remarkably parallel to those affected by splicing. Several of these differentially expressed genes are further implicated in ASD and related neurodevelopmental diseases. Weighted gene co-expression network analysis demonstrates a high degree of connectivity among these disease-related genes.
These findings highlight RBFOX1 as a key factor coordinating the regulation of both neurodevelopmentally important alternative splicing events and clinically relevant neuronal transcriptional programs in the development of human neurons.
Authors/Disclosures
Brent L. Fogel, MD, PhD, FAAN (UCLA Neurology)
PRESENTER 		Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for National Ataxia Foundation. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Ataxia Global Initiative. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Today. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Genetics. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Genetics. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Genes. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neuromarkers. The institution of Dr. Fogel has received research support from the National Institutes of Health. The institution of Dr. Fogel has received research support from the National Ataxia Foundation. The institution of an immediate family member of Dr. Fogel has received research support from the National Institutes of Health, the National Science Foundation, and the Department of Defense. The institution of Dr. Fogel has received research support from US Department of Defense .
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Neelroop Parikshak, MD, PhD (Regeneron Genetics Center) Dr. Parikshak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Maze Therapeutics.
No disclosure on file
Daniel H. Geschwind, MD, PhD (UCLA) Dr. Geschwind has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Ovid Therapeutics, Inc.. Dr. Geschwind has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for AcuraStem, Inc.. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Axial Biotherapeutics, Inc.. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Falcon Computing. Dr. Geschwind has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier-Biological Psychiatry. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NYAS. Dr. Geschwind has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Covington& Burling LLP. Dr. Geschwind has stock in none related to talk. The institution of Dr. Geschwind has received research support from CurePSP. The institution of Dr. Geschwind has received research support from NINDS. The institution of Dr. Geschwind has received research support from Rainwater Charitable Foundation. The institution of Dr. Geschwind has received research support from NIMH. The institution of Dr. Geschwind has received research support from NINDS. The institution of Dr. Geschwind has received research support from NIH. The institution of Dr. Geschwind has received research support from The Simons Foundation. The institution of Dr. Geschwind has received research support from NIH/NIMH. The institution of Dr. Geschwind has received research support from Adelson Medical Research Foundation. The institution of Dr. Geschwind has received research support from NINDS. The institution of Dr. Geschwind has received research support from NIMH. The institution of Dr. Geschwind has received research support from NINDS/NIA. The institution of Dr. Geschwind has received research support from NIH/NIMH. The institution of Dr. Geschwind has received research support from Adelson Medical Research Foundation. The institution of Dr. Geschwind has received research support from NIH/NINDS. The institution of Dr. Geschwind has received research support from NIH/NIMH. The institution of Dr. Geschwind has received research support from NIH/NIMH. The institution of Dr. Geschwind has received research support from Adelson Medical Research Foundation. The institution of Dr. Geschwind has received research support from U of Virginia and NIH/NIMH. The institution of Dr. Geschwind has received research support from NIH. The institution of Dr. Geschwind has received research support from NIH/NHGRI. The institution of Dr. Geschwind has received research support from NIH/NIMH. Dr. Geschwind has received intellectual property interests from a discovery or technology relating to health care. Dr. Geschwind has received intellectual property interests from a discovery or technology relating to health care. Dr. Geschwind has received intellectual property interests from a discovery or technology relating to health care. Dr. Geschwind has received intellectual property interests from a discovery or technology relating to health care.
Jeffrey D. Rothstein, MD, PhD (Johns Hopkins University) Dr. Rothstein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Expansion Therapeutics. Dr. Rothstein has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal Clinical Investigation. The institution of Dr. Rothstein has received research support from ALSA. The institution of Dr. Rothstein has received research support from MDA. The institution of Dr. Rothstein has received research support from F Prime. The institution of Dr. Rothstein has received research support from Target ALS. The institution of Dr. Rothstein has received research support from Chan Zuckerberg Initiative. The institution of Dr. Rothstein has received research support from Dept of Defense. Dr. Rothstein has received intellectual property interests from a discovery or technology relating to health care.