Znf703 is a novel RA target in the neural plate border
Abstract
Znf703 is an RAR- and Wnt-inducible transcription factor that exhibits a complex expression pattern in the developing embryo: Znf703 mRNA is found in the early circumblastoporal ring, then later throughout the neural plate and its border, and subsequently in the mid/hindbrain and somites. We show that Znf703 has a different and separable function in early mesoderm versus neural crest and placode development. Independent of its early knockdown phenotype on Gdf3 and Wnt8, Znf703 disrupts patterning of distinct neural crest migratory streams normally delineated by Sox10, Twist, and Foxd3 and inhibits otocyst formation and otic expression of Sox10 and Eya1. Furthermore, Znf703 promotes massive overgrowth of SOX2+ cells, disrupting the SoxB1 balance at the neural plate border. Despite prominent expression in other neural plate border-derived cranial and sensory domains, Znf703 is selectively absent from the otocyst, suggesting that Znf703 must be specifically cleared or down-regulated for proper otic development. We show that mutation of the putative Groucho-repression domain does not ameliorate Znf703 effects on mesoderm, neural crest, and placodes. We instead provide evidence that Znf703 requires the Buttonhead domain for transcriptional repression.
Additional Information
© 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 08 October 2018; Accepted 21 May 2019; Published 04 June 2019. This work was supported by grants from the National Science Foundation (IOS-0719576, IOS-1147236) to B.B. We thank Dr. Stefan Heller (Stanford University) and the Stanford Otolaryngology Imaging Core (Lars Becker) for generous use of the vibratome and confocal microscopes which were essential for Figure 7 of this manuscript. A.J. is currently supported by the A.P. Giannini Foundation. We thank Navid Zebarjadi for synthesizing the chicken Znf703 probe. Author Contributions: A.J. and B.B. conceived the experiments and wrote the manuscript. A.J., B.B. and W.T. executed all the experiments. K.A. aided in cloning the Znf703 constructs and photographing/documenting embryos. The authors declare no competing interests.Attached Files
Published - s41598-019-44722-1.pdf
Supplemental Material - 41598_2019_44722_MOESM1_ESM.pdf
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Additional details
- PMCID
- PMC6547707
- Eprint ID
- 96226
- Resolver ID
- CaltechAUTHORS:20190610-082315103
- IOS-0719576
- NSF
- IOS-1147236
- NSF
- A. P. Giannini Foundation
- Created
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2019-06-10Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field