Abstract
Meckel’s cartilage was first described by the German anatomist Johann Friedrich Meckel the Younger in 1820 from his analysis of human embryos. Two hundred years after its discovery this paper follows the development and largely transient nature of the mammalian Meckel’s cartilage, and its role in jaw development. Meckel’s cartilage acts as a jaw support during early development, and a template for the later forming jaw bones. In mammals, its anterior domain links the two arms of the dentary together at the symphysis while the posterior domain ossifies to form two of the three ear ossicles of the middle ear. In between, Meckel’s cartilage transforms to a ligament or disappears, subsumed by the growing dentary bone. Several human syndromes have been linked, directly or indirectly, to abnormal Meckel’s cartilage formation. Herein, the evolution, development and fate of the cartilage and its impact on jaw development is mapped. The review focuses on developmental and cellular processes that shed light on the mechanisms behind the different fates of this cartilage, examining the control of Meckel’s cartilage patterning, initiation and maturation. Importantly, human disorders and mouse models with disrupted Meckel’s cartilage development are highlighted, in order to understand how changes in this cartilage impact on later development of the dentary and the craniofacial complex as a whole. Finally, the relative roles of tissue interactions, apoptosis, autophagy, macrophages and clast cells in the removal process are discussed. Meckel’s cartilage is a unique and enigmatic structure, the development and function of which is starting to be understood but many interesting questions still remain.
Highlights
The developing face is created by a fusion of a number of facial processes, with the lower jaw created by cells largely from the first pharyngeal arch
After the first wave of chondrogenesis, the membranous bones form around the cartilaginous templates to create the dermatocranium, with secondary cartilages capping the bones at key points of articulation and mechanical force (Depew et al, 2002)
The main body of Meckel’s cartilage is largely transient but acts as a template for later formation of the bones of the lower jaw, with defects leading to anomalies in the pattern and size of the jaw in mouse mutants and in human embryos (Bhaskar et al, 1953; Amano et al, 2010)
Summary
The developing face is created by a fusion of a number of facial processes, with the lower jaw created by cells largely from the first pharyngeal arch. The incus, malleus and MC are initially united as a single type II collagen expressing condensation, with the incus and malleus dividing into two due to the upregulation of joint markers, creating two distinct cartilages, in a similar manner to the situation observed in the chick (Amin and Tucker, 2006; Amin et al, 2007) In the mouse this occurs at E14.5, while the incus and malleus do not fully separate until after birth in some mammals (platypus, echidna, opossum) (Anthwal et al, 2020). In other mammalian species, such as the marsupial opossum, MC sits within a groove on the medial surface of the mandible bone and TABLE 1 | Time schedule of MC development in the mouse (as the most common model of MC investigation)
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