Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation
Year: 2013
Type: preprint
Abstract: Hypocretin (orexin; Hcrt)-containing neurons of the hypothalamus are essential for the normal regulation of sleep and wake behaviors and have been implicated in feeding, anxiety, depression, and reward. The absence of these neurons causes narcolepsy in humans and model organisms. However, little is known about the molecular phenotype of these cells; previous attempts at comprehensive profiling had only limited sensitivity or were inaccurate. We generated a Hcrt translating ribosome affinity purification (bacTRAP) line for comprehensive translational profiling of all ribosome-bound transcripts in these neurons in vivo. From this profile, we identified >6000 transcripts detectably expressed above background and 188 transcripts that are highly enriched in these neurons, including all known markers of the cells. Blinded analysis of in situ hybridization databases suggests that ~60% of these are expressed in a Hcrt marker-like pattern. Fifteen of these were confirmed with double labeling and microscopy, including the transcription factor Lhx9. Ablation of this gene results in a >30% loss specifically of Hcrt neurons, without a general disruption of hypothalamic development. Polysomnography and activity monitoring revealed a profound hypersomnolence in these mice. These data provide an in-depth and accurate profile of Hcrt neuron gene expression and suggest that Lhx9 may be important for specification or survival of a subset of these cells.
Source: Genes & Development
Authors: Jasbir Dalal, Jee Hoon Roh, Susan E. Maloney, Afua Akuffo, Samir Shah, Han Yuan, Brie Wamsley, Wendell B. Jones, Cristina de Guzman Strong, Paul A. Gray, David M. Holtzman, Nathaniel Heintz, Joseph D. Dougherty
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: diamond
Funders: Howard Hughes Medical Institute, American Brain Foundation, American Academy of Neurology, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Edward Mallinckrodt, Jr. Foundation, Hope Center for Neurological Disorders, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1820417268, G245771429, Characterization of Enhancers in the Epidermal Differentiation Complex, G5138458822, G643374549, GENETIC ORGANIZATION OF RESPIRATORY CIRCUITS IN MOUSE BRAINSTEM, Washington University Intellectual and Developmental Disabilities Research Center, G758343326, Serotonin, Autism, and investigating cell types for CNS disorders., G9000032081, G9000282729, Expanding Opportunities in Genomic Research for Underrepresented Students
OpenAlex ID: W2508961482