Palatal segment contributions to midfacial anterior-posterior growth.

Ian C Welsh, Maria Feiler, Danika Lipman, Isabel Mormile, Karissa Hansen, Christopher J C Percival
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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.

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在三个近交系小鼠品系中,腭段对面中部生长的贡献。
面突融合后,腭的前后(A-P)伸长是腭形成和面中整体伸长的关键方面。上皮-间充质相互作用驱动次级腭延伸和皱纹生长区(RGZ)内周期性信号中心的形成。然而,RGZ动力学与潜在腭骨间充质前体的形态发生行为之间的关系仍然是个谜。我们的研究结果表明,RGZ的细胞活性同时驱动前副腭内上颌骨原基的褶皱形成和延伸,在腭架融合之前,其长度增加了一倍多。在RGZ后方发现的第一个形成的腭嵴代表了前副腭骨和后副腭骨前体之间一致的形态边界,在未来的上颌腭缝合处发现。这些结果提出了一个模型,其中RGZ驱动的前副腭a-P生长的变化可能会产生面前突的种间和种内差异,以及腭段相关骨骼对总腭长的比例贡献的差异。三种近交系小鼠品系的个体遗传学比较表明,虽然RGZ驱动的前副腭生长对早期面中部生长至关重要,但直到这个初始腭生长期之后,才出现对成年腭长度的细微应变特异性骨贡献。这一对正常面中部生长动力学的多方面说明证实了在腭生长的早期阶段,腭段和上颌骨之间存在一对一的关系,这可能是上颌形态进化变化的基础。此外,已确定的小鼠腭段延伸的菌株特异性差异为理解背景遗传效应对面部形态发生的影响提供了有用的基础。
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