The Mandibular and Hyoid Arches—From Molecular Patterning to Shaping Bone and Cartilage

Abstract

The mandibular and hyoid arches collectively make up the facial skeleton, also known as the viscerocranium. Although all three germ layers come together to assemble the pharyngeal arches, the majority of tissue within viscerocranial skeletal components differentiates from the neural crest. Since nearly one third of all birth defects in humans affect the craniofacial region, it is important to understand how signalling pathways and transcription factors govern the embryogenesis and skeletogenesis of the viscerocranium. This review focuses on mouse and zebrafish models of craniofacial development. We highlight gene regulatory networks directing the patterning and osteochondrogenesis of the mandibular and hyoid arches that are actually conserved among all gnathostomes. The first part of this review describes the anatomy and development of mandibular and hyoid arches in both species. The second part analyses cell signalling and transcription factors that ensure the specificity of individual structures along the anatomical axes. The third part discusses the genes and molecules that control the formation of bone and cartilage within mandibular and hyoid arches and how dysregulation of molecular signalling influences the development of skeletal components of the viscerocranium. In conclusion, we notice that mandibular malformations in humans and mice often co-occur with hyoid malformations and pinpoint the similar molecular machinery controlling the development of mandibular and hyoid arches.

Patterns of senescence and apoptosis during development of branchial arches, epibranchial placodes, and pharyngeal pouches

“…The resulting spaces between the branchial surface ectoderm and the pharyngeal endoderm are filled by mesenchyme, whose high proliferation rate is a prerequisite for the lateral outgrowth of the branchial arches. 59 Consistent with this, we found high numbers of proliferating mesenchymal and ectodermal cells in the evaginating branchial arches. However, it is likely that other mechanical factors act as counterforces F I G U R E 1 5 Immunohistochemical detection of p21 + senescent cells with two different monoclonal antibodies (HUGO-291: A, C, E, and G; F-5: B, D, F, and H) in adjacent histological sections gives virtually identical results in the branchial surface ectoderm (some cells marked with arrows) as well as in the pharyngeal endoderm of 10.5-and 11-days-old mouse embryos (E10.5 and E11).…”

Meis2 controls skeletal formation in the hyoid region

“…Nevertheless, cranial bone formation, which includes some of the most complex shapes in the vertebrate skeleton, is less understood. Both mandibular and hyoid arches give rise to sets of complex structures, practically forming the facial skeleton ( Frisdal and Trainor, 2014 ; Poopalasundaram et al, 2019 ; Fabik et al, 2021 ). However, less is known about skeletogenesis in the hyoid arch than in the mandibular arch.…”

“…Therefore, the boundary between proximal and distal hyoid arch lies in the styloid process. Worth of note, mouse mutants with mandibular anomalies often exhibit defects in the hyoid-larynx complex, suggesting a common regulatory circuit during development of the mandibular and hyoid arch ( Fabik et al, 2021 ). The idea of this common regulatory circuit is further supported by transplantation studies, where mouse dental epithelium can organize dental papilla formation in the mouse hyoid arch ( Mina and Kollar, 1987 ).…”

Neural Crest Development in Health and Disease

“…The second group contains four articles that focus on the contribution of cranial and cardiac subpopulations of neural crest cells to craniofacial [ 4 , 5 ], eye [ 6 ], and heart [ 7 ] morphogenesis. Fabik et al [ 5 ] provide a detailed review of the molecular mechanisms of craniofacial patterning and osteochondrogenesis in mouse and zebrafish embryos, also providing evidence that the morphogenesis of both mandibular and hyoid arches is governed by a shared gene regulatory network.…”

“…The second group contains four articles that focus on the contribution of cranial and cardiac subpopulations of neural crest cells to craniofacial [ 4 , 5 ], eye [ 6 ], and heart [ 7 ] morphogenesis. Fabik et al [ 5 ] provide a detailed review of the molecular mechanisms of craniofacial patterning and osteochondrogenesis in mouse and zebrafish embryos, also providing evidence that the morphogenesis of both mandibular and hyoid arches is governed by a shared gene regulatory network. By modeling and studying EFTUD2 mutation-associated mandibulofacial dysostosis with microcephaly (MFDM) syndrome in mice, Beauchamp et al [ 4 ] not only further highlight the extensive overlap between spliceosomopathies and neurocristopathies, but also unveil a new potential indirect role for P53 in alternative splicing regulation.…”