PUBLICATION

Evolutionarily conserved regulation of hypocretin neuron specification by Lhx9

Authors
Liu, J., Merkle, F.T., Gandhi, A.V., Gagnon, J.A., Woods, I.G., Chiu, C.N., Shimogori, T., Schier, A.F., Prober, D.A.
ID
ZDB-PUB-150301-6
Date
2015
Source
Development (Cambridge, England)   142(6): 1113-24 (Journal)
Registered Authors
Prober, David, Schier, Alexander, Woods, Ian G.
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cell Separation/methods*
  • Cloning, Molecular
  • DNA Primers/genetics
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation/physiology*
  • Gene Knockdown Techniques
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • High-Throughput Screening Assays/methods
  • Hypothalamus/embryology*
  • Hypothalamus/metabolism
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Mice
  • Microarray Analysis
  • Neurons/metabolism*
  • Neuropeptides/metabolism*
  • Orexins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
25725064 Full text @ Development
Abstract
Loss of neurons that express the neuropeptide hypocretin (Hcrt) has been implicated in narcolepsy, a debilitating disorder characterized by excessive daytime sleepiness and cataplexy. Cell replacement therapy, using Hcrt-expressing neurons generated in vitro, is a potentially useful therapeutic approach, but factors sufficient to specify Hcrt neurons are unknown. Using zebrafish as a high-throughput system to screen for factors that can specify Hcrt neurons in vivo, we identified the LIM homeobox transcription factor Lhx9 as necessary and sufficient to specify Hcrt neurons. We found that Lhx9 can directly induce hcrt expression and we identified two potential Lhx9 binding sites in the zebrafish hcrt promoter. Akin to its function in zebrafish, we found that Lhx9 is sufficient to specify Hcrt-expressing neurons in the developing mouse hypothalamus. Our results elucidate an evolutionarily conserved role for Lhx9 in Hcrt neuron specification that improves our understanding of Hcrt neuron development.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes