PUBLICATION

A vertebrate-conserved cis -regulatory module for targeted expression in the main hypothalamic regulatory region for the stress response

Authors
Gutierrez-Triana, J., Herget, U., Lichtner, P., Castillo-Ramírez, L.A., Ryu, S.
ID
ZDB-PUB-141128-2
Date
2014
Source
BMC Developmental Biology   14: 41 (Journal)
Registered Authors
Herget, Ulrich, Ryu, Soojin
Keywords
none
MeSH Terms
  • Hypothalamo-Hypophyseal System/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Conserved Sequence
  • Gene Expression
  • Organ Specificity
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Stress, Physiological*
  • Animals
  • Hydrocortisone/metabolism
  • Hypothalamus/metabolism*
  • Enhancer Elements, Genetic
  • Zebrafish/genetics*
  • Pituitary-Adrenal System/metabolism
(all 15)
PubMed
25427861 Full text @ BMC Dev. Biol.
Abstract
BackgroundThe homeodomain transcription factor orthopedia (Otp) is an evolutionarily conserved regulator of neuronal fates. In vertebrates, Otp is necessary for the proper development of different regions of the brain and is required in the diencephalon to specify several hypothalamic cell types, including the cells that control the stress response. To understand how this widely expressed transcription factor accomplishes hypothalamus-specific functions, we performed a comprehensive screening of otp cis-regulatory regions in zebrafish.ResultsHere, we report the identification of an evolutionarily conserved vertebrate enhancer module with activity in a restricted area of the forebrain, which includes the region of the hypothalamus that controls the stress response. This region includes neurosecretory cells producing Corticotropin-releasing hormone (Crh), Oxytocin (Oxt) and Arginine vasopressin (Avp), which are key components of the stress axis. Lastly, expression of the bacterial nitroreductase gene under this specific enhancer allowed pharmacological attenuation of the stress response in zebrafish larvae.ConclusionVertebrates share many cellular and molecular components of the stress response and our work identified a striking conservation at the cis-regulatory level of a key hypothalamic developmental gene. In addition, this enhancer provides a useful tool to manipulate and visualize stress-regulatory hypothalamic cells in vivo with the long-term goal of understanding the ontogeny of the stress axis in vertebrates.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
avphd12Tgstandard conditionsProtruding-mouth to Day 5ISH
avphd12Tgstandard conditionsProtruding-mouth to Day 5ISH
cckahd12Tgstandard conditionsProtruding-mouth to Day 5ISH
cckahd12Tgstandard conditionsProtruding-mouth to Day 5ISH
crhbhd12Tgstandard conditionsProtruding-mouth to Day 5ISH
crhbhd12Tgstandard conditionsProtruding-mouth to Day 5ISH
GFPhd12Tgstandard conditionsProtruding-mouth to Day 5Not DetectedIHC
GFPhd12Tgstandard conditionsProtruding-mouth to Day 5IFL
GFPhd12Tgstandard conditionsProtruding-mouth to Day 5IHC
GFPhd12Tgstandard conditionsDay 5IHC
1 - 10 of 32
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Phenotype
Fish Conditions Stage Phenotype Figure
hd14Tgchemical treatment: metronidazoleDay 6
hd14Tgchemical treatment: metronidazoleDay 6
1 - 2 of 2
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hd12TgTransgenic Insertion
    hd13TgTransgenic Insertion
      hd14TgTransgenic Insertion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        No data available
        Fish
        Fish
        hd12Tg
        hd13Tg
        hd14Tg
        1 - 3 of 3
        Show
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab1-avppolyclonalRabbit
        Ab3-oxtpolyclonalRabbit
        Ab6-thpolyclonalRabbit
        1 - 3 of 3
        Show
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        DsRedEFGDsRed
        GFPEFGGFP
        NTREFGNTR
        RFPEFGRFP
        1 - 4 of 4
        Show
        Mapping
        No data available
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        Citation
        Gutierrez-Triana, J., Herget, U., Lichtner, P., Castillo-Ramírez, L.A., Ryu, S. (2014) A vertebrate-conserved cis -regulatory module for targeted expression in the main hypothalamic regulatory region for the stress response. BMC Developmental Biology. 14:41.