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)
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
-
- 3,402
- views
-
- 617
- downloads
-
- 59
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
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
- Genetics and Genomics
Repurposing of pleiotropic factors during execution of diverse cellular processes has emerged as a regulatory paradigm. Embryonic development in metazoans is controlled by maternal factors deposited in the egg during oogenesis. Here, we explore maternal role(s) of Caspar (Casp), the Drosophila orthologue of human Fas-associated factor-1 (FAF1) originally implicated in host-defense as a negative regulator of NF-κB signaling. Maternal loss of either Casp or it’s protein partner, transitional endoplasmic reticulum 94 (TER94) leads to partial embryonic lethality correlated with aberrant centrosome behavior, cytoskeletal abnormalities, and defective gastrulation. Although ubiquitously distributed, both proteins are enriched in the primordial germ cells (PGCs), and in keeping with the centrosome problems, mutant embryos display a significant reduction in the PGC count. Moreover, the total number of pole buds is directly proportional to the level of Casp. Consistently, it’s ‘loss’ and ‘gain’ results in respective reduction and increase in the Oskar protein levels, the master determinant of PGC fate. To elucidate this regulatory loop, we analyzed several known components of mid-blastula transition and identify the translational repressor Smaug, a zygotic regulator of germ cell specification, as a potential critical target. We present a detailed structure-function analysis of Casp aimed at understanding its novel involvement during PGC development.
-
- Developmental Biology
The structural integrity of the sperm is crucial for male fertility, defects in sperm head-tail linkage and flagellar axoneme are associated with acephalic spermatozoa syndrome (ASS) and the multiple morphological abnormalities of the sperm flagella (MMAF). Notably, impaired head-tail coupling apparatus (HTCA) often accompanies defects in the flagellum structure, however, the molecular mechanisms underlying this phenomenon remain elusive. Here, we identified an evolutionarily conserved coiled-coil domain-containing (CCDC) protein, CCDC113, and found the disruption of CCDC113 produced spermatozoa with disorganized sperm flagella and HTCA, which caused male infertility. Further analysis revealed that CCDC113 could bind to CFAP57 and CFAP91, and function as an adaptor protein for the connection of radial spokes, nexin-dynein regulatory complex (N-DRC), and doublet microtubules (DMTs) in the sperm axoneme. Moreover, CCDC113 was identified as a structural component of HTCA, collaborating with SUN5 and CENTLEIN to connect sperm head to tail during spermiogenesis. Together, our studies reveal that CCDC113 serve as a critical hub for sperm axoneme and HTCA stabilization in mice, providing insights into the potential pathogenesis of infertility associated with human CCDC113 mutations.
