ZFIN ID: ZDB-PUB-200229-17
Epithelial Planar Bipolarity Emerges from Notch-Mediated Asymmetric Inhibition of Emx2
Kozak, E.L., Palit, S., Miranda-Rodríguez, J.R., Janjic, A., Böttcher, A., Lickert, H., Enard, W., Theis, F.J., López-Schier, H.
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
Microarrays: GEO:GSE143663, GEO:GSE144827
MeSH Terms:
  • Animals
  • Embryo, Nonmammalian/embryology*
  • Gene Expression Regulation
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Lateral Line System/embryology*
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Receptor, Notch1/genetics*
  • Receptor, Notch1/metabolism
  • Signal Transduction
  • Transcription Factors/genetics*
  • Transcription Factors/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 32109392 Full text @ Curr. Biol.
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.