The disruption of Celf6, a gene identified by translational profiling of serotonergic neurons, results in autism-related behaviors

Joseph D. Dougherty, Susan E. Maloney, David F. Wozniak, Michael A. Rieger, Lisa Sonnenblick, Giovanni Coppola, Nathaniel G. Mahieu, Juliet Zhang, Jinlu Cai, Gary J. Patti, Brett S. Abrahams, Daniel H. Geschwind, Nathaniel Heintz

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The immense molecular diversity of neurons challenges our ability to understand the genetic and cellular etiology of neuropsychiatric disorders. Leveraging knowledge from neurobiology may help parse the genetic complexity: identifying genes important for a circuit that mediates a particular symptom of a disease may help identify polymorphisms that contribute to risk for the disease as a whole. The serotonergic system has long been suspected in disorders that have symptoms of repetitive behaviors and resistance to change, including autism. We generated a bacTRAP mouse line to permit translational profiling of serotonergic neurons. From this, we identified several thousand serotonergic-cell expressed transcripts, of which 174 were highly enriched, including all known markers of these cells. Analysis of common variants near the corresponding genes in the AGRE collection implicated the RNA binding protein CELF6 in autism risk. Screening for rare variants in CELF6 identified an inherited premature stop codon in one of the probands. Subsequent disruption of Celf6 in mice resulted in animals exhibiting resistance to change and decreased ultrasonic vocalization as well as abnormal levels of serotonin in the brain. This work provides a reproducible and accurate method to profile serotonergic neurons under a variety of conditions and suggests a novel paradigm for gaining information on the etiology of psychiatric disorders.

Original languageEnglish (US)
Pages (from-to)2732-2753
Number of pages22
JournalJournal of Neuroscience
Volume33
Issue number7
DOIs
StatePublished - Feb 13 2013

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Serotonergic Neurons
Autistic Disorder
Aptitude
RNA-Binding Proteins
Neurobiology
Nonsense Codon
Ultrasonics
Genes
Psychiatry
Serotonin
Neurons
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Dougherty, J. D., Maloney, S. E., Wozniak, D. F., Rieger, M. A., Sonnenblick, L., Coppola, G., ... Heintz, N. (2013). The disruption of Celf6, a gene identified by translational profiling of serotonergic neurons, results in autism-related behaviors. Journal of Neuroscience, 33(7), 2732-2753. https://doi.org/10.1523/JNEUROSCI.4762-12.2013

The disruption of Celf6, a gene identified by translational profiling of serotonergic neurons, results in autism-related behaviors. / Dougherty, Joseph D.; Maloney, Susan E.; Wozniak, David F.; Rieger, Michael A.; Sonnenblick, Lisa; Coppola, Giovanni; Mahieu, Nathaniel G.; Zhang, Juliet; Cai, Jinlu; Patti, Gary J.; Abrahams, Brett S.; Geschwind, Daniel H.; Heintz, Nathaniel.

In: Journal of Neuroscience, Vol. 33, No. 7, 13.02.2013, p. 2732-2753.

Research output: Contribution to journalArticle

Dougherty, JD, Maloney, SE, Wozniak, DF, Rieger, MA, Sonnenblick, L, Coppola, G, Mahieu, NG, Zhang, J, Cai, J, Patti, GJ, Abrahams, BS, Geschwind, DH & Heintz, N 2013, 'The disruption of Celf6, a gene identified by translational profiling of serotonergic neurons, results in autism-related behaviors', Journal of Neuroscience, vol. 33, no. 7, pp. 2732-2753. https://doi.org/10.1523/JNEUROSCI.4762-12.2013
Dougherty, Joseph D. ; Maloney, Susan E. ; Wozniak, David F. ; Rieger, Michael A. ; Sonnenblick, Lisa ; Coppola, Giovanni ; Mahieu, Nathaniel G. ; Zhang, Juliet ; Cai, Jinlu ; Patti, Gary J. ; Abrahams, Brett S. ; Geschwind, Daniel H. ; Heintz, Nathaniel. / The disruption of Celf6, a gene identified by translational profiling of serotonergic neurons, results in autism-related behaviors. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 7. pp. 2732-2753.
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