Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues
- Institut Pasteur, France
- Brno University of Technology, Czech Republic
- University of Utah, United States
- Aix-Marseille Université, France
Abstract
In vertebrates, head and trunk muscles develop from different mesodermal populations and are regulated by distinct genetic networks. Neck muscles at the head-trunk interface remain poorly defined due to their complex morphogenesis and dual mesodermal origins. Here, we use genetically modified mice to establish a 3D model that integrates regulatory genes, cell populations and morphogenetic events that define this transition zone. We show that the evolutionary conserved cucullaris-derived muscles originate from posterior cardiopharyngeal mesoderm, not lateral plate mesoderm, and we define new boundaries for neural crest and mesodermal contributions to neck connective tissue. Furthermore, lineage studies and functional analysis of Tbx1- and Pax3-null mice reveal a unique developmental program for somitic neck muscles that is distinct from that of somitic trunk muscles. Our findings unveil the embryological and developmental requirements underlying tetrapod neck myogenesis and provide a blueprint to investigate how muscle subsets are selectively affected in some human myopathies.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Elizabeth M Sefton
Shahragim Tajbakhsh
Funding
Institut Pasteur
- Eglantine Heude
- Alexandre Grimaldi
- Shahragim Tajbakhsh
National Institutes of Health
- Elizabeth M Sefton
- Gabrielle Kardon
Agence Nationale de la Recherche
- Eglantine Heude
- Alexandre Grimaldi
- Shahragim Tajbakhsh
Centre National de la Recherche Scientifique
- Eglantine Heude
- Estelle Jullian
- Noritaka Adachi
- Alexandre Grimaldi
- Robert G Kelly
- Shahragim Tajbakhsh
Association Française contre les Myopathies
- Eglantine Heude
- Alexandre Grimaldi
- Shahragim Tajbakhsh
Central European Institute of Technology
- Marketa Tesarova
- Tomas Zikmund
- Jozef Kaiser
March of Dimes Foundation
- Elizabeth M Sefton
- Gabrielle Kardon
Fondation pour la Recherche Médicale
- Estelle Jullian
- Noritaka Adachi
- Robert G Kelly
Fondation Leducq
- Estelle Jullian
- Noritaka Adachi
- Robert G Kelly
Yamada Science Foundation
- Noritaka Adachi
- Robert G Kelly
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animals were handled as per European Community guidelines and the ethics committee of the Institut Pasteur (CTEA) approved protocols. (APAFIS#6354-20160809l2028839)
Reviewing Editor
- Clare Blackburn, MRC Centre for Regenerative Medicine, University of Edinburgh, United Kingdom
Publication history
- Received: July 17, 2018
- Accepted: November 17, 2018
- Accepted Manuscript published: November 19, 2018 (version 1)
- Version of Record published: December 28, 2018 (version 2)
Copyright
© 2018, Heude 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.
Metrics
-
- 2,857
- Page views
-
- 543
- Downloads
-
- 39
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues
eLife 7:e40179.
https://doi.org/10.7554/eLife.40179
Further reading
-
- Developmental Biology
- Stem Cells and Regenerative Medicine
Cell-free DNA (cfDNA) present in the bloodstream or other bodily fluids holds potential as a non-invasive diagnostic for early disease detection. However, it remains unclear what cfDNA markers might be produced in response to specific tissue-level events. Organoid systems present a tractable and efficient method for screening cfDNA markers. However, research investigating the release of cfDNA from organoids is limited. Here, we present a scalable method for high-throughput screening of cfDNA from cardiac organoids. We demonstrate that cfDNA is recoverable from cardiac organoids, and that cfDNA release is highest early in differentiation. Intriguingly, we observed that the fraction of cell-free mitochondrial DNA appeared to decrease as the organoids developed, suggesting a possible signature of cardiac organoid maturation, or other cardiac growth-related tissue-level events. We also observe alterations in the prevalence of specific genomic regions in cardiac organoid-derived cfDNA at different timepoints during growth. In addition, we identify cfDNA markers that were increased upon addition of cardiotoxic drugs, prior to the onset of tissue demise. Together, these results indicate that cardiac organoids may be a useful system towards the identification of candidate predictive cfDNA markers of cardiac tissue development and demise.
-
- Developmental Biology
- Neuroscience
Fenestrated and blood-brain barrier (BBB)-forming endothelial cells constitute major brain capillaries, and this vascular heterogeneity is crucial for region-specific neural function and brain homeostasis. How these capillary types emerge in a brain region-specific manner and subsequently establish intra-brain vascular heterogeneity remains unclear. Here, we performed a comparative analysis of vascularization across the zebrafish choroid plexuses (CPs), circumventricular organs (CVOs), and retinal choroid, and show common angiogenic mechanisms critical for fenestrated brain capillary formation. We found that zebrafish deficient for Gpr124, Reck, or Wnt7aa exhibit severely impaired BBB angiogenesis without any apparent defect in fenestrated capillary formation in the CPs, CVOs, and retinal choroid. Conversely, genetic loss of various Vegf combinations caused significant disruptions in Wnt7/Gpr124/Reck signaling-independent vascularization of these organs. The phenotypic variation and specificity revealed heterogeneous endothelial requirements for Vegfs-dependent angiogenesis during CP and CVO vascularization, identifying unexpected interplay of Vegfc/d and Vegfa in this process. Mechanistically, expression analysis and paracrine activity-deficient vegfc mutant characterization suggest that endothelial cells and non-neuronal specialized cell types present in the CPs and CVOs are major sources of Vegfs responsible for regionally restricted angiogenic interplay. Thus, brain region-specific presentations and interplay of Vegfc/d and Vegfa control emergence of fenestrated capillaries, providing insight into the mechanisms driving intra-brain vascular heterogeneity and fenestrated vessel formation in other organs.
