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

Abstract

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.