The Posterior Part Influences the Anterior Part of the Mouse Cranial Base Development

The cranial base is a critical structure in the head, which is composed of endoskeletal and dermal skeletal. The braincase floor, part of the cranial base, is a midline structure of the head. Because it is a midline structure connecting the posterior skull with the facial region, braincase floor is critical for the orientation of the facial structure. Shortened braincase floor leads to mid‐facial hypoplasia and malocclusions. During embryonic development, elongation of the braincase floor occurs through endochondral ossification in the parachordal cartilage, hypophyseal cartilage, and trabecular cartilage, which leads to formation of basioccipital (BO), basisphenoid (BS), and presphenoid (PS) bones, respectively. Currently, little is known about whether maturation of parachordal cartilage, hypophyseal cartilage, and trabecular cartilage occurs in a simultaneous or sequential manner and if the formation of one impacts the others. Our previous studies demonstrated that loss of function of ciliary protein Evc2 leads to premature fusion in the intersphenoid synchondrosis (ISS). In this study, we take advantage of Evc2 mutant mice to delineate the mechanism governing synchondrosis formation. Our analysis supports a cascade mechanism on the spatiotemporal regulation of the braincase floor development that the hypertrophy of parachordal cartilage (posterior side) impacts the hypertrophy of hypophyseal cartilage (middle) and trabecular cartilage (anterior side) in a sequential manner. The cascade mechanism well explains the premature fusion of the ISS in Evc2 mutant mice and is instructive to understand the specifically shortened anterior end of the braincase floor in various types of genetic syndromes. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.