Cell identity switching regulated by retinoic acid signaling maintains homogeneous segments in the hindbrain
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AbstractThe patterning of tissues to form subdivisions with distinct and homogeneous regional identity is potentially disrupted by cell intermingling. Transplantation studies suggest that homogeneous segmental identity in the hindbrain is maintained by identity switching of cells that intermingle into another segment. We show that switching occurs during normal development and is mediated by feedback between segment identity and the retinoic acid degrading enzymes, cyp26b1 and cyp26c1. egr2, which specifies the segmental identity of rhombomeres r3 and r5, underlies the lower expression level of cyp26b1 and cyp26c1 in r3 and r5 compared with r2, r4, and r6. Consequently, r3 or r5 cells that intermingle into adjacent segments encounter cells with higher cyp26b1/c1 expression, which we find is required for downregulation of egr2b expression. Furthermore, egr2b expression is regulated in r2, r4, and r6 by non-autonomous mechanisms that depend upon the number of neighbors that express egr2b. These findings reveal that a community regulation of retinoid signaling maintains homogeneous segmental identity.
CitationAddison, M., Xu, Q., Cayuso, J. and Wilkinson, D.G. (2018) Cell identity switching regulated by retinoic acid signaling maintains homogeneous segments in the hindbrain. Developmental Cell, 45(5), pp. 606-620.
PubMed ID29731343 (pubmed)
Description© 2018 The Authors. Published by Elsevier. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.devcel.2018.04.003
SponsorsThis work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK ( FC001217 ), the UK Medical Research Council ( FC001217 ), and the Wellcome Trust ( FC001217).
Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution 4.0 International
- Cell Identity Switching Regulated by Retinoic Acid Signaling Maintains Homogeneous Segments in the Hindbrain.
- Authors: Addison M, Xu Q, Cayuso J, Wilkinson DG
- Issue date: 2018 Jun 4
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