PUBLICATION

Dopaminergic neuronal cluster size is determined during early forebrain patterning

Authors
Russek-Blum, N., Gutnick, A., Nabel-Rosen, H., Blechman, J., Staudt, N., Dorsky, R.I., Houart, C., and Levkowitz, G.
ID
ZDB-PUB-080922-13
Date
2008
Source
Development (Cambridge, England)   135(20): 3401-3413 (Journal)
Registered Authors
Blechman, Janna, Dorsky, Richard, Gutnick, Amos, Houart, Corinne, Levkowitz, Gil, Nabel-Rosen, Helit, Russek-Blum, Niva, Staudt, Nicole
Keywords
Cell number, Neuronal specification, Oxytocin, Dopamine, Cell lineage
MeSH Terms
  • Animals
  • Body Patterning*
  • Cell Count
  • Cell Proliferation
  • Dopamine/physiology*
  • Embryo, Nonmammalian
  • Models, Biological
  • Neurons/cytology
  • Neurons/metabolism
  • Neurons/physiology*
  • Prosencephalon/embryology
  • Prosencephalon/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
(all 17)
PubMed
18799544 Full text @ Development
Abstract
We have explored the effects of robust neural plate patterning signals, such as canonical Wnt, on the differentiation and configuration of neuronal subtypes in the zebrafish diencephalon at single-cell resolution. Surprisingly, perturbation of Wnt signaling did not have an overall effect on the specification of diencephalic fates, but selectively affected the number of dopaminergic (DA) neurons. We identified the DA progenitor zone in the diencephalic anlage of the neural plate using a two-photon-based uncaging method and showed that the number of non-DA neurons derived from this progenitor zone is not altered by Wnt attenuation. Using birthdating analysis, we determined the timing of the last cell division of DA progenitors and revealed that the change in DA cell number following Wnt inhibition is not due to changes in cell cycle exit kinetics. Conditional inhibition of Wnt and of cell proliferation demonstrated that Wnt restricts the number of DA progenitors during a window of plasticity, which occurs at primary neurogenesis. Finally, we demonstrated that Wnt8b is a modulator of DA cell number that acts through the Fz8a (Fzd8a) receptor and its downstream effector Lef1, and which requires the activity of the Fezl (Fezf2) transcription factor for this process. Our data show that the differential response of distinct neuronal populations to the Wnt signal is not a simple interpretation of their relative anteroposterior position. This study also shows, for the first time, that diencephalic DA population size is modulated inside the neural plate much earlier than expected, concomitant with Wnt-mediated regional patterning events.
Genes / Markers
Marker Marker Type Name
barhl2GENEBarH-like homeobox 2
dkk1bGENEdickkopf WNT signaling pathway inhibitor 1b
elavl3GENEELAV like neuron-specific RNA binding protein 3
fezf2GENEFEZ family zinc finger 2
fzd8aGENEfrizzled class receptor 8a
hcrtGENEhypocretin (orexin) neuropeptide precursor
lef1GENElymphoid enhancer-binding factor 1
oxtGENEoxytocin
slc6a3GENEsolute carrier family 6 member 3
sst1.1GENEsomatostatin 1, tandem duplicate 1
1 - 10 of 12
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Figures
Figure Gallery (13 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
m808
    Point Mutation
    ot1TgTransgenic Insertion
      sb1TgTransgenic Insertion
        sb3TgTransgenic Insertion
          x8
            Deficiency
            1 - 5 of 5
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            fzd8aMO1-fzd8aMRPHLNO
            lef1MO2-lef1MRPHLNO
            wnt8bMO2-wnt8bMRPHLNO
            1 - 3 of 3
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            Fish
            Antibodies
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            GFPEFGGFP
            RFPEFGRFP
            1 - 2 of 2
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            Mapping
            No data available