PUBLICATION

Inhibition of neurogenesis at the zebrafish midbrain-hindbrain boundary by the combined and dose-dependent activity of a new hairy/E(spl) gene pair

Authors
Ninkovic, J., Tallafuss, A., Leucht, C., Topczewski, J., Tannhäuser, B., Solnica-Krezel, L., and Bally-Cuif, L.
ID
ZDB-PUB-041216-3
Date
2005
Source
Development (Cambridge, England)   132(1): 75-88 (Journal)
Registered Authors
Bally-Cuif, Laure, Leucht, Christoph, Ninkovic, Jovica, Solnica-Krezel, Lilianna, Tallafuss, Alexandra, Topczewski, Jacek
Keywords
Hairy, E(spl), her5, him, Midbrain-hindbrain, MHB, Neurogenesis, Zebrafish
MeSH Terms
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/physiology*
  • Immunoprecipitation
  • In Situ Hybridization
  • Rhombencephalon/embryology*
  • Amino Acid Sequence
  • Molecular Sequence Data
  • RNA, Messenger/metabolism
  • Two-Hybrid System Techniques
  • Phylogeny
  • Transgenes
  • Reverse Transcriptase Polymerase Chain Reaction
  • Basic Helix-Loop-Helix Transcription Factors
  • Cloning, Molecular
  • Protein Binding
  • Gene Expression Regulation, Developmental*
  • Nerve Tissue Proteins/physiology*
  • Blotting, Western
  • Animals
  • DNA Primers/chemistry
  • RNA/metabolism
  • Mesencephalon/embryology*
  • Body Patterning
  • Neurons/metabolism
  • Neurons/pathology*
  • Neurons/physiology
  • Transcription Factors/biosynthesis
  • Transcription Factors/physiology*
  • Immunohistochemistry
  • Zebrafish
(all 30)
PubMed
15590746 Full text @ Development
Abstract
The intervening zone (IZ) is a pool of progenitor cells located at the midbrain-hindbrain boundary (MHB) and important for MHB maintenance, midbrain-hindbrain growth and the generation of midbrain-hindbrain neurons. Recently, we implicated the Hairy/E(spl) transcription factor Her5 in the formation of the medial (most basal) part of the IZ (MIZ) in zebrafish; the molecular bases for lateral IZ (LIZ) formation, however, remain unknown. We now demonstrate that her5 is physically linked to a new family member, him, displaying an identical MHB expression pattern. Using single and double knockdowns of him and her5, as well as a him+her5 deletion mutant background (b404), we demonstrate that Him and Her5 are equally necessary for MIZ formation, and that they act redundantly in LIZ formation in vivo. We show that these processes do not involve cross-regulation between Him and Her5 expression or activities, although Him and Her5 can heterodimerize with high affinity. Increasing the function of one factor when the other is depleted further shows that Him and Her5 are functionally interchangeable. Together, our results demonstrate that patterning and neurogenesis are integrated by the her5-him gene pair to maintain a progenitor pool at the embryonic MHB. We propose a molecular mechanism for this process where the global `Him+Her5' activity inhibits ngn1 expression in a dose-dependent manner and through different sensitivity thresholds along the medio-lateral axis of the neural plate.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b404
    		Unknown
    m119
      		Point Mutation
      sb1TgTransgenic Insertion
        ti282a
          		Point Mutation
          tu29a
            		Point Mutation
            1 - 5 of 5
            Show
            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            her5MO1-her5MRPHLNO
            1 - 1 of 1
            Show
            Fish
            Fish
            AB
            AB + MO1-her5
            fgf8ati282a/ti282a
            gpc4b404 (AB)
            gpc4m119/m119 (AB)
            pax2atu29a/tu29a
            sb1Tg
            1 - 7 of 7
            Show
            Antibodies
            No data available
            Orthology
            No data available
            Engineered Foreign Genes
            No data available
            Mapping
            Entity Type Entity Symbol Location
            GENEher5Chr: 14 Details
            GENEher11Chr: 14 Details
            1 - 2 of 2
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            Citation
            Ninkovic, J., Tallafuss, A., Leucht, C., Topczewski, J., Tannhäuser, B., Solnica-Krezel, L., and Bally-Cuif, L. (2005) Inhibition of neurogenesis at the zebrafish midbrain-hindbrain boundary by the combined and dose-dependent activity of a new hairy/E(spl) gene pair. Development (Cambridge, England). 132(1):75-88.