PUBLICATION

Epithelial Planar Bipolarity Emerges from Notch-Mediated Asymmetric Inhibition of Emx2

Authors
Kozak, E.L., Palit, S., Miranda-Rodríguez, J.R., Janjic, A., Böttcher, A., Lickert, H., Enard, W., Theis, F.J., López-Schier, H.
ID
ZDB-PUB-200229-17
Date
2020
Source
Current biology : CB   30(6): 1142-1151.e6 (Journal)
Registered Authors
Lopez-Schier, Hernan
Keywords
diffusion pseudotime, hair cells, planar polarity, single-cell RNA sequencing
Datasets
GEO:GSE143663, GEO:GSE144827
MeSH Terms
  • Embryo, Nonmammalian/embryology*
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Receptor, Notch1/genetics*
  • Receptor, Notch1/metabolism
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Transcription Factors/genetics*
  • Transcription Factors/metabolism
  • Signal Transduction
  • Animals
  • Gene Expression Regulation
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Lateral Line System/embryology*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
(all 17)
PubMed
32109392 Full text @ Curr. Biol.
Abstract
Most plane-polarized tissues are formed by identically oriented cells [1, 2]. A notable exception occurs in the vertebrate vestibular system and lateral-line neuromasts, where mechanosensory hair cells orient along a single axis but in opposite directions to generate bipolar epithelia [3-5]. In zebrafish neuromasts, pairs of hair cells arise from the division of a non-sensory progenitor [6, 7] and acquire opposing planar polarity via the asymmetric expression of the polarity-determinant transcription factor Emx2 [8-11]. Here, we reveal the initial symmetry-breaking step by decrypting the developmental trajectory of hair cells using single-cell RNA sequencing (scRNA-seq), diffusion pseudotime analysis, lineage tracing, and mutagenesis. We show that Emx2 is absent in non-sensory epithelial cells, begins expression in hair-cell progenitors, and is downregulated in one of the sibling hair cells via signaling through the Notch1a receptor. Analysis of Emx2-deficient specimens, in which every hair cell adopts an identical direction, indicates that Emx2 asymmetry does not result from auto-regulatory feedback. These data reveal a two-tiered mechanism by which the symmetric monodirectional ground state of the epithelium is inverted by deterministic initiation of Emx2 expression in hair-cell progenitors and a subsequent stochastic repression of Emx2 in one of the sibling hair cells breaks directional symmetry to establish planar bipolarity.
Genes / Markers
Figures
No images available
Show all Figures
Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
atoh1aemx2idc5/idc5standard conditionsDay 6 to Days 7-13RNA-Seq
atoh1aWTstandard conditionsDay 6 to Days 7-13RNA-Seq
atoh1aWTstandard conditionsDay 6 to Days 7-13RNA-Seq
atoh1bvo8Tgstandard conditionsDay 6 to Days 7-13RNA-Seq
cldnbemx2idc5/idc5standard conditionsDay 6 to Days 7-13RNA-Seq
cldnbWTstandard conditionsDay 6 to Days 7-13RNA-Seq
cldnbWTstandard conditionsDay 6 to Days 7-13RNA-Seq
dldvo8Tgstandard conditionsDay 6 to Days 7-13RNA-Seq
EGFPvo8Tgstandard conditionsProtruding-mouthIFL
emx2emx2idc5/idc5standard conditionsDay 6 to Days 7-13RNA-Seq
1 - 10 of 45
Show
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fh282
    		Point Mutation
    hzm15TgTransgenic Insertion
      hzm16TgTransgenic Insertion
        hzm17
          		Indel
          hzm18
            		Indel
            idc5
              		Small Deletion
              kca3TgTransgenic Insertion
                s311tTgTransgenic Insertion
                  sqgw57AEtTransgenic Insertion
                    vo8TgTransgenic Insertion
                      1 - 10 of 10
                      Show
                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      emx2CRISPR1-emx2CRISPR
                      emx2CRISPR6-emx2CRISPR
                      emx2CRISPR4-emx2CRISPR
                      emx2CRISPR5-emx2CRISPR
                      notch1aCRISPR3-notch1aCRISPR
                      notch1aCRISPR4-notch1aCRISPR
                      notch1aCRISPR5-notch1aCRISPR
                      notch1aCRISPR6-notch1aCRISPR
                      1 - 8 of 8
                      Show
                      Fish
                      Fish
                      emx2idc5/idc5
                      emx2idc5/idc5; vo8Tg
                      sqgw57AEt
                      vo8Tg
                      WT
                      1 - 5 of 5
                      Show
                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab1-emx2polyclonalRabbit
                      1 - 1 of 1
                      Show
                      Orthology
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      EGFPEFGEGFP
                      GAL4EFGGAL4
                      1 - 2 of 2
                      Show
                      Mapping
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                      Citation
                      Kozak, E.L., Palit, S., Miranda-Rodríguez, J.R., Janjic, A., Böttcher, A., Lickert, H., Enard, W., Theis, F.J., López-Schier, H. (2020) Epithelial Planar Bipolarity Emerges from Notch-Mediated Asymmetric Inhibition of Emx2. Current biology : CB. 30(6):1142-1151.e6.