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Epithelial fusion is critical in palatogenesis, and incomplete fusion results in various type of facial cleft, depending on the region that fails to fuse. In mammalian palatogenesis, the bilateral secondary palatal processes fuse in the middle of the face to form the secondary palate. Later, the dorsal side of the secondary palatal shelves fuses with the nasal septum to complete palatogenesis. Importantly, the anterior border of the secondary palatal shelf fuses with the primary palate, which is located at the anterior and ventral border of the nasal septum. While numerous studies have investigated the mechanism of fusion between secondary palatal shelves, very little is known about how the primary palate touches and fuses with the secondary palatal shelves. In this study, we investigate the possible epithelial cell behaviors on the surface of the primary palate using palatal explant cultures of K14-GFP mice. A time-lapse observation of the GFP-labeled epithelium and an SEM analysis revealed that the extrusion epithelium appeared at the region corresponding to the fusing area and expanded rostrally on the nasal septum surface in the absence of the secondary palatal processes. Unlike on the secondary palate surface, cellular migration and subsequent autonomous mesenchymal exposure were not evident on the nasal septum or the primary palate. TUNEL staining revealed that these extrusion epithelia were undergoing apoptosis. These findings indicated that extrusion with apoptosis was autonomously initiated at the presumptive region of the fusion without contact with the opposing secondary palate.

Palatal fusion is a critical step during palatogenesis. In this fusing interface, the epithelial sheets need to be removed in order to achieve mesenchymal continuity. Epithelial cellular migration is one of the possible mechanisms, and live imaging of the labeled epithelium could provide direct evidence for it. However, the removal of medial edge epithelium (MEE) between the bilateral processes takes place in the middle of the dorso-ventral axis of the palatal shelf, and thus it is challenging to capture the cellular behavior directly. Here, we evaluate cellular behavior of MEE cells using a live imaging technique with a mouse model which expresses GFP under the promoter of Keratin14 (K14-GFP) and unpaired palatal shelf culture. Using this approach, we successfully obtained live images of epithelial behavior and detected epithelial cell migration on the surface of the secondary palatal shelf without touching of the opposing shelf. Additionally, the pattern of epithelial elimination resulted in oval-shaped exposed mesenchyme, which recapitulated the situation during secondary palate fusion in vivo. Detailed image processing revealed that most of the MEE migrated in an outward direction at the boundary regions as the oval shape of the exposed mesenchyme expanded. The migration was preceded by the bulging of MEE, and disappearance of GFP signals was not evident in bulging or migrating MEE at the boundary regions. Furthermore, the MEE migration and the subsequent mesenchymal exposure were disturbed by application of ROCK inhibitor. Together, these findings indicated that epithelial cell migration contributed importantly to the MEE removal and the subsequent exposure of the underlying mesenchyme. Furthermore, they indicated that the migration of epithelial cells was regulated in a time- and space-specific manner, since unpaired palatal shelf culture exhibited these cellular behaviors even in the absence of the opposing shelf. Altogether, present data indicated that this new experimental system combining live imaging with GFP-labeled epithelium mice and unpaired palatal shelf culture enabled direct visualization of cellular migration of MEE in vitro and could be a powerful tool to investigate its cellular and molecular mechanisms.

Purpose: Cleft lip and/or palate (CLP) is one of the most frequent craniofacial defects that could happen in 1/500 to 1/1000 live birth depending on different racial background. Among different patterns of facial cleft, complete bilateral cleft lip and palate (BCLP) is one of the most challenging cases for orthodontic and surgeons because of their deformed maxillary dental arch and severe skeletal discrepancy. It is also well known that CLP could occur as part of the phenotype in certain congenital diseases. However, from its extremely diversified phenotypic combination, some of the cases that we encounter remains difficult to diagnose. From these reasons, it is important to continuously report the outcome of orthodontic treatment in such cases which exhibit syndromic phenotypes with CLP. Material and Methods: In the present case report, an 18-year-old man with complete bilateral cleft lip and palate, skeletal Class III and open-bite with maxillary constriction, in addition to hypospadias, bubonocele, opisthotonus, and hypertonia was treated with edgewise appliance therapy combined with orthognathic surgery. The treatment began with surgically assisted rapid palatal expansion (SARPE) in anteroposterior and transverse dimensions with a three-way expander to increase the maxillary anteroposterior length and width. After the expansion, the patient underwent Le Fort I osteotomy and bilateral sagittal split osteotomy to correct skeletal Class III and open bite. Results and Conclusion: At the end of the surgical and orthodontic treatments, functional occlusion and an improved facial profile were achieved. We also discuss his diverse general phenotype due to his congenital disease. [ABSTRACT FROM AUTHOR]

Purpose: Due to the expanding demand for adult orthodontics, the number of cases which require comprehensive dental management is increasing. Adult orthodontic patients can exhibit multiple missing and/or heavily restored teeth, which could lead to an unusual extraction pattern for treatment. However, there is little existing evidence about adult orthodontic treatment of patients who present with irregular extraction. In the present report, we introduce a case with successful treatment outcome for complex problems, including anteroposterior skeletal discrepancy with multiple missing and heavily restored permanent teeth. Material and methods: The patient was a 23-year-old woman case with skeletal discrepancy which required orthognathic surgery for correction. For her comprehensive dental condition, we decided to orthodontically close the spaces of her missing upper left first molar and her extracted lower left first molar. The upper space closure required sinus lift and bone graft to supply sufficient alveolar bone for tooth movement. The lower space was closed by sectional osteotomy at the time two jaw orthognathic surgeries were performed to correct her skeletal discrepancy. Results and conclusion: At the end of the surgical and orthodontic treatments, functional occlusion and an improved facial profile were achieved. This case report provides new evidence and treatment procedures for patients who require a complex extraction pattern with orthognathic surgery. [ABSTRACT FROM AUTHOR]

Orthodontic treatment in patients with orofacial cleft such as cleft lip and palate or isolated cleft palate is challenging, especially when the patients exhibit severe maxillary growth retardation. To correct this deficiency, maxillary expansion and protraction can be performed in the first phase of orthodontic treatment. However, in some cases, the malocclusion cannot be corrected by these procedures, and thus, skeletal discrepancy remains when the patients are adolescents. These remaining problems occasionally require various orthognathic treatments according to the degree of the discrepancy. Here, we describe one case of a female with isolated cleft palate and hand malformation who exhibited severe maxillary deficiency until her adolescence and was treated with multiple orthognathic surgeries, including surgically assisted maxillary expansion (surgically assisted rapid palatal expansion), LeFort I osteotomy, and bilateral sagittal split osteotomy in order to correct severe skeletal discrepancy and malocclusion. The treatment resulted in balanced facial appearance and mutually protected occlusion with good stability. The purpose of this case report is to show the orthodontic treatment outcome of 1 patient who exhibited isolated cleft palate and subsequent severe skeletal deformities and malocclusion which was treated by an orthodontic-surgical approach. [ABSTRACT FROM AUTHOR]