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The RNA-binding protein Celf6 is highly expressed in diencephalic nuclei and neuromodulatory cell populations of the mouse brain


The gene CUG-BP, Elav-like factor 6 (CELF6) appears to be important for proper functioning of neurocircuitry responsible for behavioral output. We previously discovered that polymorphisms in or near CELF6 may be associated with autism spectrum disorder (ASD) in humans and that the deletion of this gene in mice results in a partial ASD-like phenotype. Here, to begin to understand which circuits might mediate these behavioral disruptions, we sought to establish in what structures, with what abundance, and at which ages Celf6 protein is present in the mouse brain. Using both a knockout-validated antibody to Celf6 and a novel transgenic mouse line, we characterized Celf6 expression in the mouse brain across development. Celf6 gene products were present early in neurodevelopment and in adulthood. The greatest protein expression was observed in distinct nuclei of the diencephalon and neuromodulatory cell populations of the midbrain and hindbrain, with clear expression in dopaminergic, noradrenergic, histaminergic, serotonergic and cholinergic populations, and a variety of presumptive peptidergic cells of the hypothalamus. These results suggest that disruption of Celf6 expression in hypothalamic nuclei may impact a variety of behaviors downstream of neuropeptide activity, while disruption in neuromodulatory transmitter expressing areas such as the ventral tegmental area, substantia nigra, raphe nuclei and locus coeruleus may have far-reaching influences on overall brain activity.

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Dorsal motor nucleus of vagus


Oculomotor nucleus


A12 dopamine cells


A13 dopamine cells


A14 dopamine cells


Accumbens nucleus


Accumbens nucleus, core


Accumbens nucleus, shell


Anterior hypothalamic area, anterior part


Ambiguus nucleus


Arcuate hypothalamic nucleus


Primary auditory cortex


Secondary auditory cortex, dorsal area


Secondary auditory cortex, ventral area


Caudoputamen (striatum)


Dorsomedial hypothalamic nucleus


Dorsal raphe nucleus


Edinger–Westphal nucleus


Globus pallidus


Nucleus of the horizontal limb of the diagonal band


Inferior olivary nucleus


Locus coeruleus


Laterodorsal tegmental nucleus


Lateral hypothalamic area


Lateral habenular nucleus


Lacunosum moleculare layer of the hippocampus


Lateral preoptic area


Lateral reticular nucleus


Medial habenular nucleus


Median raphe nucleus


Medial preoptic area


Medial septal nucleus


Medial tuberal nucleus


Medial vestibular nucleus, magnocellular part


Paraventricular hypothalamic nucleus


Periaqueductal gray


Posterodorsal tegmental nucleus


Periventricular hypothalamic nucleus


Pontine reticular nucleus, caudal part


Pedunculotegmental nucleus


Paraventricular thalamic nucleus


Radiatum layer of the hippocampus


Raphe magnus nucleus


Raphe obscurus nucleus


Raphe pallidus nucleus


Substantia innominata


Substantia innominata, basal part


Substantia nigra, compact part


Supraoptic nucleus


Temporal association cortex


Primary visual cortex, binocular area


Nucleus of the vertical limb of the diagonal band


Ventrolateral preoptic nucleus


Ventral tegmental area


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The authors would like to thank Arthur Loewy, Paul Gray, Nathaniel Heintz, and Cristina de Guzman Strong for equipment, reagents and discussion. We would also like to thank Heifen Feng, Juliet Zhang, and Afua Akuffo for technical assistance. Funding was provided by R21MH099798, DA038458-01, R00NS067239 to JDD, and an ACE network grant R01MH100027.

Conflict of interest

None of the authors has any established or potential conflict of interest to declare in relation with the current work.

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Correspondence to Joseph D. Dougherty.

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Maloney, S.E., Khangura, E. & Dougherty, J.D. The RNA-binding protein Celf6 is highly expressed in diencephalic nuclei and neuromodulatory cell populations of the mouse brain. Brain Struct Funct 221, 1809–1831 (2016). https://doi.org/10.1007/s00429-015-1005-z

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  • Celf6
  • Neuromodulatory
  • Diencephalon
  • Development
  • Protein expression
  • Immunohistochemistry