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.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Dalal J,Roh JH,Maloney SE,Akuffo A,Shah S,Yuan H,Wamsley B,Jones WB,de Guzman Strong C,Gray PA,Holtzman DM,Heintz N,Dougherty JDdoi
10.1101/gad.207654.112subject
Has Abstractpub_date
2013-03-01 00:00:00pages
565-78issue
5eissn
0890-9369issn
1549-5477pii
gad.207654.112journal_volume
27pub_type
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