Abstract
Anterior-posterior (A-P) elongation of the palate is a critical aspect of integrated midfacial morphogenesis. Reciprocal epithelial-mesenchymal interactions drive secondary palate elongation that is coupled to the periodic formation of signaling centers within the rugae growth zone (RGZ). However, the relationship between RGZ-driven morphogenetic processes, the differentiative dynamics of underlying palatal bone mesenchymal precursors, and the segmental organization of the upper jaw has remained enigmatic. A detailed ontogenetic study of these relationships is important because palatal segment growth is a critical aspect of normal midfacial growth, can produce dysmorphology when altered, and is a likely basis for evolutionary differences in upper jaw morphology. We completed a combined whole mount gene expression and morphometric analysis of normal murine palatal segment growth dynamics and resulting upper jaw morphology. Our results demonstrated that the first formed palatal ruga (ruga 1), found just posterior to the RGZ, maintained an association with important nasal, neurovascular and palatal structures throughout early midfacial development. This suggested that these features are positioned at a proximal source of embryonic midfacial directional growth. Our detailed characterization of midfacial morphogenesis revealed a one-to-one relationship between palatal segments and upper jaw bones during the earliest stages of palatal elongation. Growth of the maxillary anlage within the anterior secondary palate is uniquely coupled to RGZ-driven morphogenesis. This may help drive the unequaled proportional elongation of the anterior secondary palate segment prior to palatal shelf fusion. Our results also demonstrated that the future maxillary-palatine suture, approximated by the position of ruga 1 and consistently associated with the palatine anlage, formed predominantly via the posterior differentiation of the maxilla within the expanding anterior secondary palate. Our ontogenetic analysis provides a novel and detailed picture of the earliest spatiotemporal dynamics of intramembranous midfacial skeletal specification and differentiation within the context of the surrounding palatal segment A-P elongation and associated rugae formation.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Abbreviations: anterior-posterior (A-P), cranial neural crest (CNC), frontonasal process (FNP), High resolution episcopic microscopy (HREM), maxillary processes (MxP), medial nasal processes (mnp), micro-computed tomography (μCT), rugae growth zone (RGZ), transcription factors (TFs), Whole mount in situ hybridization (WISH)
Analyses of inter-strain comparisons have been removed from this version of the manuscript.