Epithelial Planar Bipolarity Emerges from Notch-Mediated Asymmetric Inhibition of Emx2
Kozak EL, Palit S, Miranda-Rodriguez JR, Janjic A, Boettcher A, Lickert H, Enard W, Theis FJ, Lopez-Schier H (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 30
Pages Range: 1142-1151.e6
Journal Issue: 6
DOI: 10.1016/j.cub.2020.01.027
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.
Involved external institutions
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
How to cite
APA:
Kozak, E.L., Palit, S., Miranda-Rodriguez, J.R., Janjic, A., Boettcher, A., Lickert, H.,... Lopez-Schier, H. (2020). Epithelial Planar Bipolarity Emerges from Notch-Mediated Asymmetric Inhibition of Emx2. Current Biology, 30(6), 1142-1151.e6. https://doi.org/10.1016/j.cub.2020.01.027
MLA:
Kozak, Eva L., et al. "Epithelial Planar Bipolarity Emerges from Notch-Mediated Asymmetric Inhibition of Emx2." Current Biology 30.6 (2020): 1142-1151.e6.
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