Maxillary Prominences Research Articles

Single-Stage Posterior Vomerine Ostectomy, Premaxillary Setback, Bilateral Gingivoperiosteoplasties and Primary Bilateral Cheiloplasty in Patients with Protuberant Premaxilla.

Various patients with complete bilateral cleft lip and palate present with a protruded premaxilla. Several techniques have been described for correctional repair of the projection with a plethora of unsatisfactory outcomes. This poses a challenge not only for the cleft team providing care but also for the patients and their respective families. Multiple patients suffer from residual deformities after inadequate primary repair, which increase surgical, financial, and psychological burden. Premaxillary setback with posterior vomerine ostectomy and complete bilateral cleft lip repair can promote alignment of the premaxilla with the maxillary prominences. To effectively address this challenging deformity, we describe a single-stage surgical technique that includes vomerine ostectomy posterior to the vomero-premaxillary suture, bilateral gingivoperiosteoplasties with complete bilateral cleft lip repair, and primary cleft rhinoplasty. Careful surgical planning is essential for adequate matching between the length of the protruded premaxilla and the extent of ostectomy. The described technique offers several advantages for the management of complete bilateral cleft lip with a projected premaxilla. It can be applied anywhere around the world and is most beneficial in underprivileged areas where patients suffer from restricted access to healthcare, absence of presurgical orthodontics and lack of sufficient resources.

Grainyhead-like 2 interacts with noggin to regulate tissue fusion in mouse.

Defective tissue fusion during mammalian embryogenesis results in congenital anomalies, such as exencephaly, spina bifida and cleft lip and/or palate. The highly conserved transcription factor grainyhead-like 2 (Grhl2) is a crucial regulator of tissue fusion, with mouse models lacking GRHL2 function presenting with a fully penetrant open cranial neural tube, facial and abdominal clefting (abdominoschisis), and an open posterior neuropore. Here, we show that GRHL2 interacts with the soluble morphogen protein and bone morphogenetic protein (BMP) inhibitor noggin (NOG) to impact tissue fusion during development. The maxillary prominence epithelium in embryos lacking Grhl2 shows substantial morphological abnormalities and significant upregulation of NOG expression, together with aberrantly distributed pSMAD5-positive cells within the neural crest cell-derived maxillary prominence mesenchyme, indicative of disrupted BMP signalling. Reducing this elevated NOG expression (by generating Grhl2-/-;Nog+/- embryos) results in delayed embryonic lethality, partial tissue fusion rescue, and restoration of tissue form within the craniofacial epithelia. These data suggest that aberrant epithelial maintenance, partially regulated by noggin-mediated regulation of BMP-SMAD pathways, may underpin tissue fusion defects in Grhl2-/- mice.

Automatic detection of nostril and key markers in images

In the medical field, one of complex challenges in surgery involving the skin, cartilage, mucosa, and the skeletal platform is the cleft nasal deformity. The causes of deformity are nasal formed from improper fusion of the medial and lateral nasal prominences with the maxillary prominence during embryologic development. Primary rhinoplasty or first time of cleft nose repair is the nasal surgery for repairing the cleft nasal deformity. In post cheiloplasty, the primary rhinoplasty patients must use nasal splint for supporting surgical wound. However, regular nasal splints are expensive and only come with default nasal size. This limits nasal splint from supporting specific patient cases such as children. The goal of this study is to implement a program that can automatically detect the nostril and green marker in patient images for creating custom-made 3D nasal splints. The proposed method is created utilizing the CNN model. YOLO architecture is utilized because it is the one of several CNN architectures that works well with the face recognition task. The YOLOV5, YOLOV8, and YOLO-NAS are attempted and compared in the training phase. The model with a highest performance is selected, and fine-tuned for adjusting to be compatible with a patient dataset. The fine-tuned YOLOV8 reaches a mAP with 99.5%. The predicted images from fine-tuned model are used to perform body part segmentation like Otsu's thresholding and discover contour to locate essential features like the green marker and nostril in ellipse and bounding boxes. The nostril distance is calculated using the bounding box and ellipse. The columella distance or nostril gap is measured from the distance between nostrils in YOLO predicted label. Both distances are converted into centimeter scale and evaluated with ground truth value in volunteer and patient cases from nasal expert for inspecting efficiency between bounding box, ellipse, and size of marker. The result proves that the proposed model can detect crucial features with mean absolute error 0.102. Furthermore, the proposed model indicates that marker size has no effect on detection and distance, according to the findings of the experiments.

Prevalence, trend, and associated risk factors for cleft lip with/without cleft palate: a national study on live births from 2016 to 2021

BackgroundsCleft lip with or without cleft palate (CL/P) is the most common congenital craniofacial anomaly, including non-syndromic cleft lip with or without cleft palate and cleft palate only. Failure in the fusion of median and lateral nasal processes, the maxillary prominence, and soft tissues around the oral cavity can cause CL/P. Previously, the prevalence has been estimated to be 1 among every 1000 births in 2014 among American neonates and no other reports have been available since. Thus, this study aimed to calculate the prevalence and trend of isolated CL/P among American live births from 2016 to 2021 with its associated risk factors.Methods and materialsIn this cross-sectional population-based retrospective study, we used live birth data provided by the National Center for Health Statistics (NCHS) from the Center for Disease Control and Prevention (CDC). We calculated the prevalence per 10,000 live births of isolated (non-syndromic) CL/P from 2016 to 2021. To examine risk factors for developing isolated CL/P, we used logistic regression modelling.ResultsThe total prevalence per 10,000 births from 2016 to 2021 was 4.88 (4.79–4.97), for both sexes, and 5.96 (5.82–6.10) for males, and 3.75 (3.64–3.87) for females. The prevalence did not show any consistent linear decreasing or increasing pattern. We found significant association between increased odds of developing isolated CL/P among cases with 20 to 24 year-old mothers (OR = 1.07, 1.01–1.13, p = 0.013), mothers who smoked 11 to 20 cigarettes per day (OR = 1.46, 1.33–1.60, p < 0.001), mothers with extreme obesity (OR = 1.32, 1.21–1.43, p < 0.001), mothers with grade II obesity (OR = 1.32, 1.23–1.42, p < 0.001), mothers with pre-pregnancy hypertension (OR = 1.17, 1.04–1.31, p = 0.009), mothers with pre-pregnancy diabetes mellitus (OR = 1.96, 1.71–2.25, p < 0.001), and mothers who used assisted reproductive technology (OR = 1.40, 1.18–1.66, p < 0.001).ConclusionsOur findings suggest a minuscule increase, albeit insignificant, in the trend of CL/P prevalence from 2016 to 2021. Developing CL/P had greater odds among mothers with pre-pregnancy diabetes, smoking, obesity, and pre-pregnancy hypertension mothers along with mothers who used assisted reproductive technology. Isolated CL/P had the highest prevalence in non-Hispanic Whites, American Indian or Alaskan Native and Native Hawaiian and Other Pacific Islanders.

Perception of vibration threshold potential with tuning fork and pure tone audiometry assessment for early detection of diabetic polyneuropathy

Background: Diabetes mellitus (DM), a multisystem disorder, is a known etiological entity, leading to several neurological disorders. Among them, nervous system is more commonly affected. In most of the diabetic polyneuropathy cases, sensory symptoms involving both general and special senses predominate. Due to gradual and non-homogenous manifestations, it is not easy to detect its onset. Till now no accepted gold standard has been available for its assessment and diagnosis. In this study, changes in vibration perception threshold (VPT) at different frequencies and auditory perception threshold have been investigated in diabetes patients and healthy controls. Aims and objectives: Determination of perception threshold of a general sense-vibration sense and a special sense-hearing in normal human subjects and patients of DM and evaluation of perception threshold of the human sensory system by VPT test and pure tone audiometry (PTA) as a diagnostic, prognostic and research tool for diabetic neuropathy. Materials and Methods: A case–control study, conducted in the department of physiology at medical college, Kolkata, after obtaining approval by the institutional research and ethics committee on 100 cases and 40 control subjects. Testing of vibration sensitivity was performed with the help of tuning forks of frequencies of 128 Hz, 256 Hz, and 512 Hz. Assessment of auditory perception threshold was done by Siemens SD 28 diagnostic audiometer. Results: All data obtained by the methods described here are tabulated. Graphs and charts are drawn and analyzed by standard statistical methods using Statistical Packages for the Social Sciences (version-16) and MATLAB (version-9). A P &lt; 0.05 was considered as significant. A partial negative correlation was observed between the vibration sensitivity and fasting blood sugar and postprandial blood sugar level of the patient population of DM cases, with a “r” value (Pearson’s correlation coefficient was around −0.5. By PTA, it was found the percentage of rise in auditory threshold is around 92–93% in 8000 Hz frequency, and the results of the t-test yield a very highly significant difference (P &lt; 0.0001) between cases and controls. It was found that 128 Hz and 256 Hz vibration stimuli applied over maxillary prominence are highly sensitive and efficient tools for perception analysis. Pure tone auditory threshold evaluation showed preservation of the right-sided advantage of auditory sensitivity and frequency-dependent loss of hearing in the diabetic study population. Conclusion: Determination of perception threshold of vibration sense by tuning fork and auditory perception by PTA may be used as an effective, easily performed, and low-cost bedside and also outpatient department-based diagnostic tool in patients with DM.

Retinoic acid delays murine palatal shelf elevation by inhibiting Wnt5a-mediated noncanonical Wnt signaling and downstream Cdc-42/F-actin remodeling in mesenchymal cells.

Mammalian palatal shelves erupted from maxillary prominences undergo vertical extention, transient elevation, and horizontal growth to fuse. Previous studies in mice reported that the retinoic acid (RA) contributed to cleft palate in high incidence by delaying the elevating procedure, but little was known about the underlying biological mechanisms. In this study, hematoxylin-eosin and immunofluorescence staining were employed to evaluate the phenotypes and the expression of related markers in the RA-treated mice model. In situ hybridization and RT-qPCR were used to detect the expression of genes involved in Wnt signaling pathway. The palatal mesenchymal cells were cultured in vitro, and stimulated with RA or CASIN, and co-treated with Foxy5. Wnt5a and Ccd42 expression were evaluated by immunofluorescence staining. Phalloidin was used to label the microfilament cytoskeleton (F-actin) in cultured cells. We revealed that RA resulted in 100% incidence of cleft palate in mouse embryos, and the expression of genes responsible for Wnt5a-mediated noncanonical Wnt signal transduction were specifically downregulated in mesenchymal palatal shelves. The in vitro study of palatal mesenchymal cells indicated that RA treatment disrupted the organized remodeling of cytoskeleton, an indicative structure of cell migration regulated by the small Rho GTPase Cdc42. Moreover, we showed that the suppression of cytoskeleton and cell migration induced by RA was partially restored using the small molecule Foxy-5-mediated activation of Wnt5A, and this restoration was attenuated by CASIN (a selective GTPase Cdc42 inhibitor) again. These data identified a crucial mechanism for Wnt5a-mediated noncanonical Wnt signaling in acting downstream of Rho GTPase Cdc42 to regulate cytoskeletal remodeling and cell migration during the process of palate elevation. Our study provided a new explanation for the cause of cleft palate induced by RA.

Developmental origin of the mammalian premaxilla

The evolution of jaws has played a major role in the success of vertebrate expansion into a wide variety of ecological niches. A fundamental, yet unresolved, question in craniofacial biology is about the origin of the premaxilla, the most distal bone present in the upper jaw of all amniotes. Recent reports have suggested that the mammalian premaxilla is derived from embryonic maxillary prominences rather than the frontonasal ectomesenchyme as previously shown in studies of chicken embryos. However, whether mammalian embryonic frontonasal ectomesenchyme contributes to the premaxillary bone has not been investigated and a tool to trace the contributions of the frontonasal ectomesenchyme to facial structures in mammals is lacking. The expression of the Alx3 gene is activated highly specifically in the frontonasal ectomesenchyme, but not in the maxillary mesenchyme, from the beginning of facial morphogenesis in mice. Here, we report the generation and characterization of a novel Alx3CreERT2 knock-in mouse line that express tamoxifen-inducible Cre DNA recombinase from the Alx3 locus. Tamoxifen treatment of Alx3CreERT2/+;Rosa26mTmG/+ embryos at E7.5, E8.5, E9.5, and E10.5, each induced specific labeling of the embryonic medial nasal and lateral nasal mesenchyme but not the maxillary mesenchyme. Lineage tracing of Alx3CreERT2-labeled frontonasal mesenchyme from E9.5 to E16.5 clearly showed that the frontonasal mesenchyme cells give rise to the osteoblasts generating the premaxillary bone. Furthermore, we characterize a Dlx1-Cre BAC transgenic mouse line that expresses Cre activity in the embryonic maxillary but not the frontonasal mesenchyme and show that the Dlx1-Cre labeled embryonic maxillary mesenchyme cells contribute to the maxillary bone as well as the soft tissues lateral to both the premaxillary and maxillary bones but not to the premaxillary bone. These results clearly demonstrate the developmental origin of the premaxillary bone from embryonic frontonasal ectomesenchyme cells in mice and confirm the evolutionary homology of the premaxilla across amniotes.

Gene Regulatory Networks and Signaling Pathways in Palatogenesis and Cleft Palate: A Comprehensive Review.

Palatogenesis is a complex and intricate process involving the formation of the palate through various morphogenetic events highly dependent on the surrounding context. These events comprise outgrowth of palatal shelves from embryonic maxillary prominences, their elevation from a vertical to a horizontal position above the tongue, and their subsequent adhesion and fusion at the midline to separate oral and nasal cavities. Disruptions in any of these processes can result in cleft palate, a common congenital abnormality that significantly affects patient's quality of life, despite surgical intervention. Although many genes involved in palatogenesis have been identified through studies on genetically modified mice and human genetics, the precise roles of these genes and their products in signaling networks that regulate palatogenesis remain elusive. Recent investigations have revealed that palatal shelf growth, patterning, adhesion, and fusion are intricately regulated by numerous transcription factors and signaling pathways, including Sonic hedgehog (Shh), bone morphogenetic protein (Bmp), fibroblast growth factor (Fgf), transforming growth factor beta (Tgf-β), Wnt signaling, and others. These studies have also identified a significant number of genes that are essential for palate development. Integrated information from these studies offers novel insights into gene regulatory networks and dynamic cellular processes underlying palatal shelf elevation, contact, and fusion, deepening our understanding of palatogenesis, and facilitating the development of more efficacious treatments for cleft palate.

Influential Factors in the Efficacy of Hemoporfin-Mediated Photodynamic Therapy for Port-wine Stains.

Hemoporfin-mediated photodynamic therapy (HMME-PDT) is commonly used in the treatment of port-wine stains (PWS). However, the influential factors for the efficacy of the treatment are not well defined. This study intends to observe the influential factors for the efficacy of HMME-PDT in the treatment of port-wine stains (PWS). A total of 551 patients with PWS of head and neck was enrolled in this retrospective study. Further screening the patients of facial PWS, 484 patients were chosen. Patients were treated with HMME-PDT. All patients received 1~3 sessions of treatment with 2~3-month intervals. We photographed the lesions before each session and 2~3 months after the last session. Ages, sessions, lesion subtypes, and previous treatment history were related to the response of HMME-PDT (P =0.032, P<0.001, P=0.012, P=0.003 respectively). Treatment sessions were the independent factor correlated with efficacy after 3 sessions of treatment. Patients with no treatment history targeting PWS showed higher efficacy than those were treated with laser or other photodynamic treatment (P<0.05). The efficacy was higher by increasing the sessions of treatment. The efficacy was higher for lesion on maxillary prominence area and mandibular prominence area that on frontonasal prominence area and optic vesicle area (P<0.05). HMME-PDT is an effective in the treatment of PWS. Patients received no previous treatment for PWS, total treatment sessions and lesion on maxillary prominence area and mandibular prominence area are positive factors.

Increased miR-200c levels disrupt palatal fusion by affecting apoptosis, cell proliferation, and cell migration

The mammalian palate separates the oral and nasal cavities, facilitating proper feeding, respiration, and speech. Palatal shelves, composed of neural crest-derived mesenchyme and surrounding epithelium, are a pair of maxillary prominences contributing to this structure. Palatogenesis reaches completion upon the fusion of the midline epithelial seam (MES) following contact between medial edge epithelium (MEE) cells in the palatal shelves. This process entails numerous cellular and molecular occurrences, including apoptosis, cell proliferation, cell migration, and epithelial-mesenchymal transition (EMT). MicroRNAs (miRs) are small, endogenous, non-coding RNAs derived from double-stranded hairpin precursors that regulate gene expression by binding to target mRNA sequences. Although miR-200c is a positive regulator of E-cadherin, its role in palatogenesis remains unclear. This study aims to explore the role of miR-200c in palate development. Before contact with palatal shelves, mir-200c was expressed in the MEE along with E-cadherin. After palatal shelf contact, miR-200c was present in the palatal epithelial lining and epithelial islands surrounding the fusion region but absent in the mesenchyme. The function of miR-200c was investigated by utilizing a lentiviral vector to facilitate overexpression. Ectopic expression of miR-200c resulted in E-cadherin upregulation, impaired dissolution of the MES, and reduced cell migration for palatal fusion. The findings imply that miR-200c is essential in palatal fusion as it governs E-cadherin expression, cell death, and cell migration, acting as a non-coding RNA. This study may contribute to clarifying the underlying molecular mechanisms in palate formation and provides insights into potential gene therapies for cleft palate.

Treatment Plan and Discussions of Class I with Smilestream: A Case Report

The aim of the study was to present a Class I case and the treatment plan related to orthodontic diagnosis. The chief complaint of a patient and his parents are crowded teeth upper and lower and anterior crossbite. “@I’m looking like a crocodile” were the first words of the boy sitting on the dental chair. The main task was functional but also esthetics because it was from the first important to him. The treated malocclusion is characterized with a narrow maxillary width and prominence of the mandible. The maxilla was deficient in anteroposterior and transverse dimensions, causing a slightly concave and unpleasant profile, a crossbite relationship of lateral incisors and upper and lower anterior crowding. The use of mechanics was preferred and accepted as a better solution for the patient according to the idea to generate well directed growth. The patient was 12 year-old boy with Class I malocclusion and anterior crossbite. A molar and canine class 1 and correction of the malocclusion were obtained. The improvement of facial aesthetics and smile enlarging were also ensured.

Single-cell RNA-Seq reveals transcriptional regulatory networks directing the development of mouse maxillary prominence

During vertebrate embryonic development, neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial structures, such as tooth and palate. However, the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated. Here, we perform single-cell RNA-Seq to comprehensively characterize the transcriptional dynamics during mouse maxillary development from embryonic day (E) 10.5–E14.5. Our single-cell transcriptome atlas of ∼28,000 cells uncovers mesenchymal cell populations representing distinct differentiating states and reveals their developmental trajectory, suggesting that the segregation of dental from the palatal mesenchyme occurs at E11.5. Moreover, we identify a series of key transcription factors (TFs) associated with mesenchymal fate transitions and deduce the gene regulatory networks directed by these TFs. Collectively, our study provides important resources and insights for achieving a systems-level understanding of craniofacial morphogenesis and abnormality.

Effects of Dlx2 overexpression on the genes associated with the maxillary process in the early mouse embryo.

The transcription factor Dlx2 plays an important role in craniomaxillofacial development. Overexpression or null mutations of Dlx2 can lead to craniomaxillofacial malformation in mice. However, the transcriptional regulatory effects of Dlx2 during craniomaxillofacial development remain to be elucidated. Using a mouse model that stably overexpresses Dlx2 in neural crest cells, we comprehensively characterized the effects of Dlx2 overexpression on the early development of maxillary processes in mice by conducting bulk RNA-Seq, scRNA-Seq and CUT&Tag analyses. Bulk RNA-Seq results showed that the overexpression of Dlx2 resulted in substantial transcriptome changes in E10.5 maxillary prominences, with genes involved in RNA metabolism and neuronal development most significantly affected. The scRNA-Seq analysis suggests that overexpression of Dlx2 did not change the differentiation trajectory of mesenchymal cells during this development process. Rather, it restricted cell proliferation and caused precocious differentiation, which may contribute to the defects in craniomaxillofacial development. Moreover, the CUT&Tag analysis using DLX2 antibody revealed enrichment of MNT and Runx2 motifs at the putative DLX2 binding sites, suggesting they may play critical roles in mediating the transcriptional regulatory effects of Dlx2. Together, these results provide important insights for understanding the transcriptional regulatory network of Dlx2 during craniofacial development.

Variation in canine Position’s in unilateral cleft lip and palate patients - A case Series

Cleft lip/palate is a common congenital anomaly that occurs during birth. Incomplete fusion of the maxillary prominence and median nasal processes results in a small niche or indentation on the lip and palate that extends all the way up to the nose. The orofacial cleft can appear as isolated cleft lip, cleft lip with cleft palate, be associated with syndromes, or present unilaterally or bilaterally. Various management modalities are recommended depending on the extent and severity of the anomalies. Cleft lip and palate are frequently associated with developmental problems in the primary and permanent dentitions. To restore all of the aesthetic, functional, periodontal, and restorative components, it is critical to address the associated dental anomalies

Evolution of the therian face through complete loss of the premaxilla.

The anatomical framework of the jawbones is highly conserved among most of the Osteichthyes, including the tetrapods. However, our recent study suggested that the premaxilla, the rostralmost upper jaw bone, was rearranged during the evolution of therian mammals, being replaced by the septomaxilla at least in the lateral part. In the present study, to understand more about the process of evolution from the ancestral upper jaw to the therian face, we re-examined the development of the therian premaxilla (incisive bone). By comparing mouse, bat, goat, and cattle fetuses, we confirmed that the therian premaxilla has dual developmental origins, the lateral body and the palatine process. This dual development is widely conserved among the therian mammals. Cell-lineage-tracing experiments using Dlx1-CreERT2 mice revealed that the palatine process arises in the ventral part of the premandibular domain, where the nasopalatine nerve distributes, whereas the lateral body develops from the maxillary prominence in the domain of the maxillary nerve. Through comparative analysis using various tetrapods, we concluded that the palatine process should not be considered part of the ancestral premaxilla. It rather corresponds to the anterior region of the vomerine bone of nonmammalian tetrapods. Thus, the present findings indicate that the true premaxilla was completely lost during the evolution of the therian mammals, resulting in the establishment of the unique therian face as an evolutionary novelty. Reconsideration of the homological framework of the cranial skeleton based on the topographical relationships of the ossification center during embryonic development is warranted.

The role of cytoskeleton regulators in embryonic facial morphogenesis

Small GTPases are downstream of the non‐canonical WNT JNK‐PCP pathway. The most well studied members of this group are RhoA, Rac1 and CDC42. These small GTPases regulate cell shape, orientation, and migration through regulating the actomyosin cytoskeleton. In addition, components of this pathway have been linked to non‐syndromic cleft lip with or without cleft palate. The objective of this study is to test whether small GTPase signaling is required and sufficient for facial morphogenesis at stages where lip fusion is taking place.MethodsThe faces of E4.5 chicken embryos were dissected to include the two facial processes involved in lip fusion, the frontonasal and maxillary processes (Fig. 1). After a dose‐response experiment to find the optimal concentrations, the organ cultures were treated with either an antagonist of RhoA signaling (ROCKi 20µM) or an antagonist of Rac1 (Rac1i 100µM) or an agonist (RhoA/ Rac1/CDC42 activator 0.5µg/ml). Organ cultures were photographed and measured at 0 and 24hrs. Percentage growth differences were analyzed using Prism Graphpad software (v. 9.2).ResultsIn the control cultures, frontonasal mass width decreased by 23% and increased in cranio‐caudal height by 17% over 24‐hour period. The nasal slits did not change. The maxillary prominences increased in height and width by 12% and 37% respectively over 24‐hour period similar to growth in vivo. The ROCKi treated cultures prevented the narrowing of the frontonasal mass and increased the length of the nasal slits. ROCKi treatment had no effect on the height of the frontonasal mass nor maxillary prominences. In contrast, the RAC1i had no effect on facial growth. The agonist significantly reduced frontonasal mass width compared to ROCKi. In addition, the agonist significantly decreased growth of the maxillary prominences.ConclusionsThe changes in facial morphogenesis may be explained by active cytoskeletal remodeling, particularly in the RhoA pathway. We excluded a requirement for RAC1 in facial morphogenesis in our system. Our data also suggest that different regions of the face have different requirements for specific small GTPase signaling. The frontonasal mass is dependent on RhoA signaling but not the maxillary prominences. Over activation of all GTPases shows that correct levels are necessary for normal morphogenesis. Overall, we have revealed a complex interplay between small GTPAses in midfacial morphogenesis.

A Neural Crest-specific Overexpression Mouse Model Reveals the Transcriptional Regulatory Effects of Dlx2 During Maxillary Process Development.

Craniofacial morphogenesis is a complex process that requires precise regulation of cell proliferation, migration, and differentiation. Perturbations of this process cause a series of craniofacial deformities. Dlx2 is a critical transcription factor that regulates the development of the first branchial arch. However, the transcriptional regulatory functions of Dlx2 during craniofacial development have been poorly understood due to the lack of animal models in which the Dlx2 level can be precisely modulated. In this study, we constructed a Rosa26 site-directed Dlx2 gene knock-in mouse model Rosa26 CAG-LSL-Dlx2−3xFlag for conditionally overexpressing Dlx2. By breeding with wnt1 cre mice, we obtained wnt1 cre ; Rosa26 Dlx2/- mice, in which Dlx2 is overexpressed in neural crest lineage at approximately three times the endogenous level. The wnt1 cre ; Rosa26 Dlx2/- mice exhibited consistent phenotypes that include cleft palate across generations and individual animals. Using this model, we demonstrated that Dlx2 caused cleft palate by affecting maxillary growth and uplift in the early-stage development of maxillary prominences. By performing bulk RNA-sequencing, we demonstrated that Dlx2 overexpression induced significant changes in many genes associated with critical developmental pathways. In summary, our novel mouse model provides a reliable and consistent system for investigating Dlx2 functions during development and for elucidating the gene regulatory networks underlying craniofacial development.

The diagnostic ability of the Fränkel manoeuvre in detecting mandibular versus maxillary involvement in subjects with a class II discrepancy

Abstract Objective This study aimed to evaluate the ability of the Fränkel manoeuvre to identify the contributing jaw to a class II malocclusion. Methods This cross-sectional study examined 37 subjects (age range 9–13 years) who presented with a class II malocclusion and an overjet greater than 6 mm. Two profile photographs were taken of each patient, one in centric relation, and the other after executing the Fränkel manoeuvre to generate a canine and molar class I relationship. The photographs were distributed to two groups of judges who included 20 general dentists and 20 orthodontists. The level of profile aesthetics before (T0) and after (T1) the manoeuvre was determined using a 100-mm visual analogue scale, and a score of “profile improvement” was determined as T1 minus T0. The diagnostic ability of the Fränkel manoeuvre was calculated against lateral cephalometry as the reference standard, using the receiver operative characteristics (ROC) analysis. Results Twenty-six subjects had mandibular retrusion and 11 showed mandibular retrusion combined with maxillary prominence. The improvement score after the manoeuvre was significantly greater in subjects who showed a one-jaw than those with a two-jaw involvement (P &lt; 0.05). In cases that showed an improvement score ≥ 9 as judged by general dentists, or ≥ 17 as judged by orthodontists, the class II discrepancy mainly resulted from mandibular retrusion. The correspondingly lower improvement scores indicated that maxillary prognathism was involved in the class II discrepancy. Conclusion The Fränkel manoeuvre was an effective clinical method for diagnosing the contributing jaw in class II malocclusion patients.

Early Secondary Alveolar Bone Grafting and Facial Growth of Patients with Complete Unilateral Cleft Lip and Palate.

To investigate the craniofacial growth outcomes of early secondary alveolar bone grafting(ABG) around 6 years of age. Retrospective cohort study. 1 North-American and 5 Northern-European cleft centers. 33 subjects with CUCLP consecutively treated with secondary ABG around 6 years of age were compared to 105 subjects from 4 centers treated with late secondary ABG and 19 subjects from 1 center with primary ABG. Preorthodontic standardized lateral cephalometric radiographs taken after 12 years of age were traced and analyzed according to the Eurocleft Study protocol. Fourteen angular and two proportional measurements were performed. Measurement means from the Study Center(SC) were compared to 5 Northern-European centers using analysis of variance and Welch's modified t-tests, and P < .05 was considered statistically significant. For the SC, the mean age ± SD at the time of bone graft was 5.85 ± 0.71 years and the mean age at the time of the lateral cephalogram was 13.4 ± 1.8 years. The sagittal maxillary prominence of the SC was favorably comparable to the 5 Northern-European centers. The mean SNA (78.1 ± 4.3) for the SC was significantly higher compared to 4 of the 5 Northern-European centers(all P < .05), and the mean ANB angle was comparable to 4 of the 5 centers. Similarly, the mean soft tissue ANB angle was not significantly different to the 5 centers. The soft tissue vertical proportions compared favorably to all 5 Northern-European centers(all P < .01). Craniofacial growth outcomes of early secondary ABG around 6 years compare favorably to the outcomes of late secondary ABG.

Mammalian face as an evolutionary novelty

Significance The anatomical framework of the jaw has traditionally been thought to be highly conserved among vertebrates. However, here we show that the therian-unique face (muzzle) evolved via a drastic alteration of the common pattern of the tetrapod jaw. Through comparative morphological and developmental analyses, we demonstrated that the therian mammal’s premaxilla (rostral-most upper jawbone) is derived from the maxillary prominence of the mandibular arch. The developmental primordium that produces the premaxilla in nonmammalian tetrapods rarely contributes to the upper jaw in therian mammals but rather forms a motile nose. We propose that these previously unrecognized rearrangements allowed key innovations such as the highly sensitive tactile perception and olfactory function in mammalian evolution.