PUBLICATION

Notch-Mediated Determination of Hair-Bundle Polarity in Mechanosensory Hair Cells of the Zebrafish Lateral Line

Authors
Jacobo, A., Dasgupta, A., Erzberger, A., Siletti, K., Hudspeth, A.J.
ID
ZDB-PUB-191102-9
Date
2019
Source
Current biology : CB   29(21): 3579-3587.e7 (Journal)
Registered Authors
Dasgupta, Agnik, Erzberger, Anna, Hudspeth, A.J. (Jim)
Keywords
Emx2, bistability, delta, lateral inhibition, neuromast, planar cell polarity
MeSH Terms
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Receptor, Notch1/genetics*
  • Receptor, Notch1/metabolism
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Animals
  • Cell Polarity/genetics*
  • Cell Differentiation/genetics*
  • Hair Cells, Auditory/metabolism
  • Lateral Line System/physiology*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
(all 15)
PubMed
31668618 Full text @ Curr. Biol.
Abstract
The development of mechanosensory epithelia, such as those of the auditory and vestibular systems, results in the precise orientation of mechanosensory hair cells. After division of a precursor cell in the zebrafish's lateral line, the daughter hair cells differentiate with opposite mechanical sensitivity. Through a combination of theoretical and experimental approaches, we show that Notch1a-mediated lateral inhibition produces a bistable switch that reliably gives rise to cell pairs of opposite polarity. Using a mathematical model of the process, we predict the outcome of several genetic and chemical alterations to the system, which we then confirm experimentally. We show that Notch1a downregulates the expression of Emx2, a transcription factor known to be involved in polarity specification, and acts in parallel with the planar-cell-polarity system to determine the orientation of hair bundles. By analyzing the effect of simultaneous genetic perturbations to Notch1a and Emx2, we infer that the gene-regulatory network determining cell polarity includes an undiscovered polarity effector.
Genes / Markers
Figures
Figure Gallery (4 images)
Show all Figures
Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
EGFPnotch1ab420/b420; vo8Tgchemical treatment by environment: copper(II) sulfate, chemical ablation: neuromast hair cellDay 4IHC
EGFPvo8Tgstandard conditionsDay 4IHC
EGFPvo8Tgstandard conditionsDay 4IHC
EGFPvo8Tgchemical treatment by environment: copper(II) sulfate, chemical ablation: neuromast hair cellDay 4IHC
1 - 4 of 4
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Phenotype
Fish Conditions Stage Phenotype Figure
kca3Tg; ru1012Tg; vo8TgcontrolDay 4
kca3Tg; ru1012Tg; vo8TgcontrolDay 4
kca3Tg; ru1012Tg; vo8Tgstandard conditionsDay 4
notch1ab420/b420; vo8Tgstandard conditionsDay 4
vo8Tgchemical treatment by environment: copper(II) sulfate, chemical treatment by environment: LY-411575, chemical ablation: neuromast hair cellDay 4
vo8Tgchemical treatment by environment: copper(II) sulfate, chemical ablation: neuromast hair cellDay 4
1 - 6 of 6
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b420
    		Point Mutation
    b638
      		Unknown
      el515
        		Indel
        hi781TgTransgenic Insertion
        idc4TgTransgenic Insertion
          idc5
            		Small Deletion
            kca3TgTransgenic Insertion
              ru1012TgTransgenic Insertion
                tr233
                  		Point Mutation
                  tw212b
                    		Point Mutation
                    1 - 10 of 12
                    Show
                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    No data available
                    Fish
                    Fish
                    kca3Tg; ru1012Tg; vo8Tg
                    notch1ab420/b420; vo8Tg
                    TL
                    vo8Tg
                    1 - 4 of 4
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                    Antibodies
                    Name Type Antigen Genes Isotypes Host Organism
                    Ab1-dldmonoclonalIgG1Mouse
                    Ab1-emx2polyclonalRabbit
                    Ab1-mycmonoclonal
                      		IgG1Mouse
                      Ab1-sptbn1monoclonal
                        		IgG1Mouse
                        Ab2-dlcmonoclonal
                          		IgG2aMouse
                          1 - 5 of 5
                          Show
                          Orthology
                          No data available
                          Engineered Foreign Genes
                          Marker Marker Type Name
                          EGFPEFGEGFP
                          GAL4FFEFGGAL4FF
                          mCherryEFGmCherry
                          1 - 3 of 3
                          Show
                          Mapping
                          No data available
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                          Citation
                          Jacobo, A., Dasgupta, A., Erzberger, A., Siletti, K., Hudspeth, A.J. (2019) Notch-Mediated Determination of Hair-Bundle Polarity in Mechanosensory Hair Cells of the Zebrafish Lateral Line. Current biology : CB. 29(21):3579-3587.e7.