Abstract
Introduction: Surgical reconstruction is recommended for cleft palate patients. However, improper muscle reconstruction can cause scarring and velopharyngeal insufficiency. Understanding the developmental patterns of soft palatal musculature is crucial for improving treatments. Although mice are commonly used to investigate soft palate development, the uvula deficiency in mice limits their applicability. This study aimed to compare the developmental characteristics of soft palate muscles in miniature pigs and mice at various stages to better understand the patterns in large mammals. Methods: Specimens of soft palate were collected from human embryos, miniature pigs, and mice at different stages. Furthermore, comprehensive gross observations, haematoxylin and eosin staining, and immunohistochemical analyses for myosin heavy chain and hypermethylated cancer 1 (Hic1) were conducted on multiple dissected sections. Results: Mature soft palatal musculature exhibited anatomical and histological similarities across the three species. Notably, miniature pigs exhibited the uvula structure and uvula muscle (MU) development comparable to humans. Embryonic day 40 (E40, equivalent to human embryonic week 11, E11w) represented the early developmental stage of the MU, characterized by scattered muscle cells not yet coalescing into multinucleated fibres. By E45 (aligned with human E12w), the muscle bundles reached maturity, exhibiting two oriented fibre bundles flanking the midline. Levator veli palatini muscle and palatopharyngeus of miniature pigs exhibited a distinct course pattern due to the presence of the MU. Hic1+ perimysial cells were observed at the extending edge of the developing palatopharyngeus of miniature pigs, indicating a potential guiding role in the migration of myogenic cells. Conclusion: Characterized by the MU, the spatiotemporal dynamic process of soft palatal musculature of miniature pigs was revealed. Miniature pigs exhibit a similar structure of the MU to that of humans and therefore serve as a promising model for researching soft palatal musculature development of large mammals in the future.
Plain Language Summary
Cleft palate (CP) is a condition where the roof of the mouth fails to fuse. Understanding the muscle anatomy in this region is crucial for improving surgical outcomes. In this study, we focused on the development of soft palate muscles in miniature pigs and compared it with humans and mice. Since the uvula muscle (MU) is essential for proper dynamic velopharyngeal closure, we compared the anatomical characteristics of this muscle across the three species. Specifically, we documented the origin and insertion points, adjacent structures, and critical developmental stages of the MU. Comparative analysis demonstrated that miniature pigs – unlike mice – exhibit remarkable similarity to humans in terms of uvula morphology, MU development, and anatomical characteristics. We further compared interspecies anatomical differences in other muscle types between miniature pigs and mice. Our findings strongly suggest that miniature pigs represent a promising model for studying human soft palatal musculature development, which could lead to improved surgical techniques and outcomes for CP patients.
