RARγ is required for mesodermal gene expression prior to gastrulation in Xenopus
Abstract
The developing vertebrate embryo is exquisitely sensitive to retinoic acid (RA) concentration, particularly during anteroposterior patterning. In contrast to Nodal and Wnt signaling, RA was not previously considered to be an instructive signal in mesoderm formation during gastrulation. Here, we show in Xenopus that RARγ is indispensable for the expression of early mesoderm markers and is, therefore, an obligatory factor in mesodermal competence and/or maintenance. We identified several novel targets upregulated by RA receptor signaling in the early gastrula that are expressed in the circumblastoporal ring and linked to mesodermal development. Despite overlapping expression patterns of the genes encoding the RA-synthesizing enzyme Aldh1a2 and the RA-degrading enzyme Cyp26a1, RARγ1 functions as a transcriptional activator in early mesoderm development, suggesting that RA ligand is available to the embryo earlier than previously appreciated. RARγ1 is required for cellular adhesion, as revealed by spontaneous dissociation and depletion of ncam1 mRNA in animal caps harvested from RARγ1 knockdown embryos. RARγ1 knockdown obliterates somite boundaries, and causes loss of Myod protein in the presomitic mesoderm, but ectopic, persistent expression of Myod protein in the trunk. Thus, RARγ1 is required for stabilizing the mesodermal fate, myogenic commitment, somite boundary formation, and terminal skeletal muscle differentiation.
Additional Information
© 2018 Published by The Company of Biologists Ltd. Received August 21, 2017; Accepted July 31, 2018; Published 17 September 2018. We thank Dr Stefan Heller (Stanford University) for generous use of his lab's Leica VT1200 vibratome and the Stanford Otolaryngology Imaging Core (Lars Becker) for use of the Zeiss LSM700 confocal microscope, which were essential for Fig. 6 of this manuscript. The authors declare no competing or financial interests. Author contributions: Conceptualization: A.J., B.B.; Methodology: A.J., B.B.; Software: T.S.; Validation: A.J., W.T., B.B.; Formal analysis: A.J., W.T., T.S.; Investigation: A.J., W.T., T.S., B.B.; Resources: A.J., T.S., B.B.; Data curation: T.S.; Writing - original draft: A.J.; Writing - review & editing: A.J., B.B.; Visualization: A.J., W.T.; Supervision: A.J., B.B.; Project administration: A.J., B.B.; Funding acquisition: T.S., B.B. This work was supported by grants from the National Science Foundation (IOS-0719576, IOS-1147236 to B.B.). A.J. is currently supported by the A.P. Giannini Foundation. Data availability: RNA-seq data have been deposited in Gene Expression Omnibus under accession number GSE119124. Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.147769.supplemental.Attached Files
Published - dev147769.full.pdf
Supplemental Material - DEV147769supp.pdf
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Additional details
- Eprint ID
- 90405
- Resolver ID
- CaltechAUTHORS:20181024-160140657
- IOS-0719576
- NSF
- IOS-1147236
- NSF
- A. P. Giannini Foundation
- Created
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2018-10-25Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field