Hedgehog signaling patterns the oral-aboral axis of the mandibular arch
- Cincinnati Children's Hospital Medical Center, United States
- University of Colorado Anschutz Medical Campus, United States
Abstract
Development of vertebrate jaws involves patterning neural crest-derived mesenchyme cells into distinct subpopulations along the proximal-distal and oral-aboral axes. Although the molecular mechanisms patterning the proximal-distal axis have been well studied, little is known regarding the mechanisms patterning the oral-aboral axis. Using unbiased single-cell RNA-seq analysis followed by in situ analysis of gene expression profiles, we show that Shh and Bmp4 signaling pathways are activated in a complementary pattern along the oral-aboral axis in mouse embryonic mandibular arch. Tissue-specific inactivation of hedgehog signaling in neural crest-derived mandibular mesenchyme led to expansion of BMP signaling activity to throughout the oral-aboral axis of the distal mandibular arch and subsequently duplication of dentary bone in the oral side of the mandible at the expense of tongue formation. Further studies indicate that hedgehog signaling acts through the Foxf1/2 transcription factors to specify the oral fate and pattern the oral-aboral axis of the mandibular mesenchyme.
Data availability
The single-cell RNA-seq data from this study have been deposited into the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database (accession number GSE112837). All data generated or analyzed during this study are included in the manuscript and supporting files.
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Hedgehog signaling patterns the oral-aboral axis of the mandibular archNCBI Gene Expression Omnibus, GSE112837.
Article and author information
Author details
Funding
National Institutes of Health (R01 DE027046)
- Rulang Jiang
Shriners Hospitals for Children (Grant #85900)
- Rulang Jiang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Shahragim Tajbakhsh, Institut Pasteur, France
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals by the National Institutes of Health. The animal use protocol was approved by the Institutional Animal Care and Use Committee of Cincinnati Children's Hospital Medical Center (Permit Number IACUC2016-0095).
Version history
- Received: July 21, 2018
- Accepted: January 11, 2019
- Accepted Manuscript published: January 14, 2019 (version 1)
- Version of Record published: January 25, 2019 (version 2)
Copyright
© 2019, Xu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Hedgehog signaling patterns the oral-aboral axis of the mandibular arch
eLife 8:e40315.
https://doi.org/10.7554/eLife.40315
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