Cell Identity Switching Regulated by Retinoic Acid Signaling Maintains Homogeneous Segments in the Hindbrain

• Published in: Developmental cell Vol. 45; no. 5; pp. 606 - 620.e3
• Main Authors: Addison, Megan, Xu, Qiling, Cayuso, Jordi, Wilkinson, David G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04-06-2018; Cell Press
• Subjects: Animals; Antineoplastic Agents - pharmacology; Body Patterning - drug effects; boundary formation; cell identity switching; cell intermingling; Cell Lineage - drug effects; cell segregation; Cellular Reprogramming; community effect; cyp26; egr2; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - physiology; Gene Expression Regulation, Developmental - drug effects; hindbrain segmentation; Neural Crest - cytology; Neural Crest - physiology; regional identity; retinoic acid; Rhombencephalon - cytology; Rhombencephalon - drug effects; Rhombencephalon - physiology; Signal Transduction; Tretinoin - pharmacology; Zebrafish - growth & development; Zebrafish - physiology; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; regional identity; hindbrain segmentation; cell intermingling; retinoic acid; cyp26; cell segregation; cell identity switching; egr2; boundary formation; community effect
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2018.04.003

The 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.
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•Some cells intermingle between hindbrain segments and switch identity•Identity is influenced by the number of neighbors with same or different identity•Switching is mediated by feedback between segment identity and retinoid signaling•Community retinoid signaling enables maintenance of homogeneous segments
Addison et al. uncover how segments within the hindbrain maintain a homogeneous identity despite intermingling of cells at early stages. Cells that intermingle into an adjacent segment switch identity since they encounter a different level of retinoic acid signaling from their new neighbors.