PUBLICATION

Specification of hypothalamic neurons by dual regulation of the homeodomain protein Orthopedia

Authors
Blechman, J., Borodovsky, N., Eisenberg, M., Nabel-Rosen, H., Grimm, J., and Levkowitz, G.
ID
ZDB-PUB-071125-9
Date
2007
Source
Development (Cambridge, England)   134(24): 4417-4426 (Journal)
Registered Authors
Levkowitz, Gil, Nabel-Rosen, Helit
Keywords
Neural development, Dopamine, Oxytocin
MeSH Terms
  • Dopamine/metabolism
  • Animals
  • Carrier Proteins/genetics
  • Carrier Proteins/metabolism
  • Gene Expression Regulation, Developmental
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Models, Neurological
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Mutation
  • Hypothalamus/cytology
  • Hypothalamus/embryology*
  • Hypothalamus/metabolism
  • Neurons/metabolism
  • DNA Primers/genetics
  • Oxytocin/metabolism
  • Transcription Factors/genetics*
  • Transcription Factors/metabolism
  • Base Sequence
  • Receptors, Vasoactive Intestinal Peptide/genetics
  • Receptors, Vasoactive Intestinal Peptide/metabolism
  • Signal Transduction
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Oligodeoxyribonucleotides, Antisense/genetics
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I/genetics
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I/metabolism
(all 29)
PubMed
18003738 Full text @ Development
Abstract
In the developing hypothalamus, a variety of neurons are generated adjacent to each other in a highly coordinated, but poorly understood process. A critical question that remains unanswered is how coordinated development of multiple neuronal types is achieved in this relatively narrow anatomical region. We focus on dopaminergic (DA) and oxytocinergic (OT) neurons as a paradigm for development of two prominent hypothalamic cell types. We report that the development of DA and OT-like neurons in the zebrafish is orchestrated by two novel pathways that regulate the expression of the homeodomain-containing protein Orthopedia (Otp), a key determinant of hypothalamic neural differentiation. Genetic analysis showed that the G-protein-coupled receptor PAC1 and the zinc finger-containing transcription factor Fezl act upstream to Otp. In vivo and in vitro experiments demonstrated that Fezl and PAC1 regulate Otp at the transcriptional and the post-transcriptional levels, respectively. Our data reveal a new genetic network controlling the specification of hypothalamic neurons in vertebrates, and places Otp as a critical determinant underlying Fezl- and PAC1-mediated differentiation.
Genes / Markers
Figures
Figure Gallery (14 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
m808
    Point Mutation
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    adcyap1bMO2-adcyap1bMRPHLNO
    adcyap1r1bMO1-adcyap1r1bMRPHLNO
    fezf2MO2-fezf2MRPHLNO
    fezf2MO3-fezf2MRPHLNO
    otpaMO1-otpaMRPHLNO
    otpbMO5-otpbMRPHLNO
    1 - 6 of 6
    Show
    Fish
    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available