PUBLICATION

DeltaA/DeltaD Regulate Multiple and Temporally Distinct Phases of Notch Signaling during Dopaminergic Neurogenesis in Zebrafish

Authors
Mahler, J., Filippi, A., and Driever, W.
ID
ZDB-PUB-101222-13
Date
2010
Source
The Journal of neuroscience : the official journal of the Society for Neuroscience   30(49): 16621-16635 (Journal)
Registered Authors
Driever, Wolfgang, Filippi, Alida, Mahler, Julia
Keywords
none
MeSH Terms
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Oligodeoxyribonucleotides, Antisense/pharmacology
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Mutation/genetics
  • Repressor Proteins/metabolism
  • Transcription Factors/metabolism
  • Zebrafish
  • Animals, Genetically Modified
  • Ubiquitin-Protein Ligases/metabolism
  • HSP70 Heat-Shock Proteins/metabolism
  • Signal Transduction/physiology*
  • Enzyme Inhibitors/pharmacology
  • Receptors, Notch/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Animals
  • Dopamine/metabolism*
  • Embryo, Nonmammalian
  • Cell Cycle/genetics
  • Deoxyuridine/analogs & derivatives
  • Deoxyuridine/metabolism
  • Neurogenesis/physiology*
  • Brain/cytology
  • Brain/embryology
  • Brain/growth & development
  • Dipeptides/pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Corticotropin-Releasing Hormone/genetics
  • Corticotropin-Releasing Hormone/metabolism
  • Tyrosine 3-Monooxygenase/metabolism
  • Gene Expression Regulation, Developmental/genetics
  • Gene Expression Regulation, Developmental/physiology
(all 35)
PubMed
21148001 Full text @ J. Neurosci.
Abstract
Dopaminergic neurons develop at distinct anatomical sites to form some of the major neuromodulatory systems in the vertebrate brain. Despite their relevance in neurodegenerative diseases and the interests in reconstitutive therapies from stem cells, mechanisms of the neurogenic switch from precursor populations to dopaminergic neurons are not well understood. Here, we investigated neurogenesis of different dopaminergic and noradrenergic neuron populations in the zebrafish embryo. Birth-dating analysis by EdU (5-ethynyl-2'-deoxyuridine) incorporation revealed temporal dynamics of catecholaminergic neurogenesis. Analysis of Notch signaling mutants and stage-specific pharmacological inhibition of Notch processing revealed that dopaminergic neurons form by temporally distinct mechanisms: dopaminergic neurons of the posterior tuberculum derive directly from neural plate cells during primary neurogenesis, whereas other dopaminergic groups form in continuous or wavelike neurogenesis phases from proliferating precursor pools. Systematic analysis of Notch ligands revealed that the two zebrafish co-orthologs of mammalian Delta1, DeltaA and DeltaD, control the neurogenic switch of all early developing dopaminergic neurons in a partially redundant manner. DeltaA/D may also be involved in maintenance of dopaminergic precursor pools, as olig2 expression in ventral diencephalic dopaminergic precursors is affected in dla/dld mutants. DeltaA/D act upstream of sim1a and otpa during dopaminergic specification. However, despite the fact that both dopaminergic and corticotropin-releasing hormone neurons derive from sim1a- and otpa-expressing precursors, DeltaA/D does not act as a lineage switch between these two neuronal types. Rather, DeltaA/D limits the size of the sim1a- and otpa-expressing precursor pool from which dopaminergic neurons differentiate.
Genes / Markers
Figures
No images available
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hi781TgTransgenic Insertion
kca3TgTransgenic Insertion
    kca4TgTransgenic Insertion
      ta52b
        Point Mutation
        tr233
          Point Mutation
          1 - 5 of 5
          Show
          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          dlaMO2-dlaMRPHLNO
          dlbMO2-dlbMRPHLNO
          jag2bMO2-jag2bMRPHLNO
          jag2bMO3-jag2bMRPHLNO
          tp53MO4-tp53MRPHLNO
          1 - 5 of 5
          Show
          Fish
          Antibodies
          Name Type Antigen Genes Isotypes Host Organism
          Ab6-thpolyclonalRabbit
          1 - 1 of 1
          Show
          Orthology
          Engineered Foreign Genes
          Marker Marker Type Name
          GAL4EFGGAL4
          1 - 1 of 1
          Show
          Mapping