Diverse Fate of an Enigmatic Structure: 200 Years of Meckel’s Cartilage

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.

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

“…Meckel’s cartilage initially consists of a pair of continuous rods of cartilage, which subsequently elongate anteriorly and later fuse in the distal midline to form a V-shaped structure outlining the forming lower jaw in mice. In mammals, Meckel’s cartilage can be divided into three parts according to the fate of each region: anterior/distal, intermediate/central, and posterior/proximal [ 22 , 23 , 24 , 25 ]. In humans, the distal part of Meckel’s cartilage undergoes endochondral ossification and forms a portion of dentary bone extending from the mental foramen to the midline.…”

“…Since Meckel’s cartilage acts as a template for later formation of the lower jaw bones, its defects lead to anomalies in the pattern and size of the lower jaw in both mouse and human embryos [ 36 ]. In summary, Meckel’s cartilage turns into diverse structures along the proximal-distal axis: the malleus; ligaments, replaced by the dentary; and mandibular symphyseal cartilage [ 25 ].…”

Species-specific deployment of Runx2 isoforms and differential regulation of target genes during avian jaw development and evolution

“…In our study, we observe species-specific differences in expression of P1 (Figure 5A) but not P2 (Figure 5B) among chick, quail, and duck. Perhaps this is related to the fact that the lower jaw of birds ossifies exclusively through intramembranous ossification except for the proximal most region of Meckel's cartilage, which undergoes endochondral ossification but only at stages later than what we examined (Starck, 1989;Helms and Schneider, 2003;Eames et al, 2004;Mitgutsch et al, 2011;Ealba et al, 2015;Anthwal et al, 2017;Svandova et al, 2020). Other studies on activation and repression by isoforms utilizing P1 versus P2 indicate that both have similar transcriptional potentials (Banerjee et al, 2001).…”

PRDM proteins control Wnt/β-catenin activity to regulate craniofacial chondrocyte differentiation

“…Alterations to the gene regulatory networks (GRNs) and signaling modules that control craniofacial chondrocyte maturation can greatly impact the development of these cartilage elements. Changes to the development of these cartilage scaffolds can negatively affect the formation and function of subsequent bone structures and contribute to craniofacial defects including, but not limited to mandibular hypoplasia, cleft lip/palate, and middle ear defects [9][10][11][12][13][14][15][16][17][18].…”