PuSH - Publication Server of Helmholtz Zentrum München

Kozak, E.L. ; Palit, S. ; Miranda Rodriguez, J.R. ; Janjic, A.* ; Böttcher, A. ; Lickert, H. ; Enard, W.* ; Theis, F.J. ; López-Schier, H.

Epithelial planar bipolarity emerges from Notch-mediated asymmetric inhibition of Emx2.

Curr. Biol. 30, 1142-1151 (2020)
Publ. Version/Full Text Postprint Research data DOI PMC
Open Access Green
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.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Diffusion Pseudotime ; Hair Cells ; Planar Polarity ; Single-cell Rna Sequencing; Hair-cell Regeneration; Gene-expression; Myosin-vi; Polarity
ISSN (print) / ISBN 0960-9822
e-ISSN 1879-0445
Journal Current Biology
Quellenangaben Volume: 30, Issue: 6, Pages: 1142-1151 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Sensory Biology and Organogenesis (SBO)
Institute of Diabetes and Regeneration Research (IDR)
Institute of Computational Biology (ICB)
Institute of Stem Cell Research (ISF)