Ciliary Hedgehog signaling regulates cell survival to build the facial midline

Craniofacial defects are among the most common phenotypes caused by ciliopathies, yet the developmental and molecular etiology of these defects is poorly understood. We investigated multiple mouse models of human ciliopathies (including Tctn2, Cc2d2a and Tmem231 mutants) and discovered that each displays hypotelorism, a narrowing of the midface. As early in development as the end of gastrulation, Tctn2 mutants displayed reduced activation of the Hedgehog (HH) pathway in the prechordal plate, the head organizer. This prechordal plate defect preceded a reduction of HH pathway activation and Shh expression in the adjacent neurectoderm. Concomitant with the reduction of HH pathway activity, Tctn2 mutants exhibited increased cell death in the neurectoderm and facial ectoderm, culminating in a collapse of the facial midline. Enhancing HH signaling by decreasing the gene dosage of a negative regulator of the pathway, Ptch1, decreased cell death and rescued the midface defect in both Tctn2 and Cc2d2a mutants. These results reveal that ciliary HH signaling mediates communication between the prechordal plate and the neurectoderm to provide cellular survival cues essential for development of the facial midline.

Dental-Facial Midline: An Esthetic Based Classification

Background: The facial midline and dental midline play an important role in facial esthetics, cosmetic dentistry, facial plastic surgery, and anthropologic studies. Objective: This study studied the dental-facial midline in Nepalese subjects and to classify the midline. Methods: The study was conducted in 150 Nepalese subjects, mostly consisting of University students (80 males and 70 females). After obtaining ethical approval, facial and dental midlines were analyzed using a scale. Results: It showed 26 (18%) study subjects showed the coincidence of the facial midline with the maxillary and mandibular dental midlines. It showed that only 44 (30%) subjects showed the coincidence of facial midline with only maxillary dental midline, and 26 (17%) subjects showed the facial midline coincidence with only mandibular dental midline. The dental midline discrepancy was more prevalent in the maxillary arch and more prevalent on the right side. Midline discrepancy is seen more in males compared to females. The majority of the deviation showed 1 mm, followed by 2 mm, and 3 mm. Conclusion: The coincidence of the facial midline with both the maxillary and mandibular dental midlines is uncommon. Midline discrepancy is seen more in males compared to females. The majority of the subjects show a mild discrepancy of 1 mm. The midline discrepancy was more seen on the right side and in the maxillary arch.

Combined Orthodontic and Surgical Management for Treatment of Severe Class III Malocclusion with Anterior and Posterior Crossbites

Severe class III malocclusion can be a great challenge, especially in adult patients. This case report describes an adult patient with severe skeletal class III malocclusion and with an obvious maxillary deficiency and mandibular excess causing both anterior and posterior crossbites in addition to a shift in the upper and lower midlines to the left concerning the facial midline. This was complicated by compensatory mechanisms such as the proclination of upper incisors and retroclination of lower incisors. Decompensation of the upper and lower arches was performed combined with upper arch expansion to relieve crowding in the upper arch and correct the posterior crossbite. This was followed by double jaw surgeries, including Le Fort I osteotomy in the maxilla and bilateral sagittal split osteotomy (BSSO) in the mandible. Orthodontic finishing procedures were then used to correct any other dental discrepancies. Remarkable esthetic and functional results were achieved with high patient satisfaction.

Dental-Facial Midline: An Esthetic Based Classification

BackgroundThe facial midline and dental midline play an important role in facial esthetics, cosmetic dentistry, facial plastic surgery, and anthropologic studies.ObjectivesThis study studied the dento-facial midline in Nepalese subjects and to classify the midline.MethodsThe study was done in 150 Nepalese subjects, mostly consisting of University students (70 males and 80 females). After obtaining ethical approval, facial and dental midlines were analyzed using a scale.ResultsIt showed 24 (16%) study subjects showed the coincidence of the facial midline with the maxillary and mandibular dental midlines. It showed that only 26 (16 %) subjects showed the coincidence of facial midline with only maxillary dental midline and 17 (11 %) subjects showed the facial midline coincidence with only mandibular dental midline. The dental midline discrepancy was more prevalent in the maxillary arch and more prevalent on the right side. Midline discrepancy is seen more in males compared to females. The majority of the deviation showed 1 mm, followed by 2 mm, and 3 mm.ConclusionsThe coincidence of the facial midline with both the maxillary and mandibular dental midlines is uncommon. Midline discrepancy is seen more in males compared to females. The majority of the subjects show a mild discrepancy of 1 mm. The midline discrepancy was more seen on the right side and in the maxillary arch.

Symmetry and fluctuation of cell movements in neural crest-derived facial mesenchyme

In the face, symmetry is established when bilateral streams of neural crest cells leave the neural tube at the same time, follow identical migration routes and then give rise to the facial prominences. However developmental instability exists, particularly surrounding the steps of lip fusion. The causes of instability are unknown but inability to cope with developmental fluctuations are a likely cause of congenital malformations such as non-syndromic orofacial clefts. Here, we tracked cell movements over time in the frontonasal mass which forms the facial midline and participates in lip fusion using live-cell imaging. Our mathematical examination of cell velocity vectors uncovered temporal fluctuations in several parameters including order/disorder, symmetry/asymmetry and divergence/convergence. We found that treatment with a RhoGTPase inhibitor completely disrupted the temporal fluctuations in all measures and blocked morphogenesis. Thus we discovered that genetic control of symmetry extends to mesenchymal cell movements and that these movements are of the type that could be perturbed in in asymmetrical malformations such as non-syndromic cleft lip.

Ciliary Hedgehog signaling regulates cell survival to build the facial midline

Craniofacial defects are among the most common phenotypes caused by ciliopathies, yet the developmental and molecular etiology of these defects is poorly understood. We investigated multiple mouse models of human ciliopathies (including Tctn2, Cc2d2a and Tmem231 mutants) and discovered that each displays hypotelorism, a narrowing of the midface. As early in development as the end of gastrulation, Tctn2 mutants displayed reduced activation of the Hedgehog (HH) pathway in the prechordal plate, the head organizer. This prechordal plate defect preceded a reduction of HH pathway activation and Shh expression in the adjacent neurectoderm. Concomitant with the reduction of HH pathway activity, Tctn2 mutants exhibited increased cell death in the neurectoderm and facial ectoderm, culminating in a collapse of the facial midline. Enhancing HH signaling by decreasing the gene dosage of a negative regulator of the pathway, Ptch1, decreased cell death and rescued the midface defect in both Tctn2 and Cc2d2a mutants. These results reveal that ciliary HH signaling mediates communication between the prechordal plate and the neurectoderm to provide cellular survival cues essential for development of the facial midline.

Dental-Facial Midline: An Esthetic Based Classification

Background: The facial midline and dental midline play an important role in facial esthetics, cosmetic dentistry, facial plastic surgery, and anthropologic studies. Objective: This study studied the dental-facial midline in Nepalese subjects and to classify the midline. Methods: The study was conducted in 150 Nepalese subjects, mostly consisting of University students (80 males and 70 females). After obtaining ethical approval, facial and dental midlines were analyzed using a scale. Results: It showed 26 (18%) study subjects showed the coincidence of the facial midline with the maxillary and mandibular dental midlines. It showed that only 44 (30%) subjects showed the coincidence of facial midline with only maxillary dental midline, and 26 (17%) subjects showed the facial midline coincidence with only mandibular dental midline. The dental midline discrepancy was more prevalent in the maxillary arch and more prevalent on the right side. Midline discrepancy is seen more in males compared to females. The majority of the deviation showed 1 mm, followed by 2 mm, and 3 mm. Conclusion: The coincidence of the facial midline with both the maxillary and mandibular dental midlines is uncommon. Midline discrepancy is seen more in males compared to females. The majority of the subjects show a mild discrepancy of 1 mm. The midline discrepancy was more seen on the right side and in the maxillary arch.

Application of a Novel Automatic Method for Determining the Bilateral Symmetry Midline of the Facial Skeleton Based on Invariant Moments

Assuming a symmetric pattern plays a fundamental role in the diagnosis and surgical treatment of facial asymmetry, for reconstructive craniofacial surgery, knowing the precise location of the facial midline is important since for most reconstructive procedures the intact side of the face serves as a template for the malformed side. However, the location of the midline is still a subjective procedure, despite its importance. This study aimed to automatically locate the bilateral symmetry midline of the facial skeleton based on an invariant moment technique using pseudo-Zernike moments. A total of 367 skull images were evaluated using the proposed technique. The technique was found to be reliable and provided good accuracy in the symmetry planes. This new technique will be utilized for subsequent studies to evaluate diverse craniofacial reconstruction techniques.

Evaluation of Facial and Dental Midline Discrepancies in Nepalese Population

Introduction: The facial midline is defined by the landmark such as the nose, philtrum, and chin aligned in a straight line. It should be in the center of the face and should coincide with the dental midline. But clinically it is often observed that some discrepancies exist between facial and dental midlines. Thus the aim of this study was to evaluate the facial and dental midline discrepancies. Methods: A total of 300 subjects, 150 male and 150 female from People’s Dental College and Hospital were selected. Full facial view standardized photograph with a posed smile with teeth in occlusion was taken with Canon 400D digital SLR. For standardized measurement vertical metallic scale with millimeter, markings were placed on the right side of the patient in all cases. The software program Digimizer image analysis (version 4.6.1) was used to determine the facial and maxillary dental midline. Result: This study showed 6.66% of male and 12% of female had perfectly coinciding F1 facial midline (perpendicular from the midpoint of inner canthus distance), F2 facial midline (line joining the midpoint of inner canthus and the midpoint of the base of the nose) and maxillary midline. 26% of males and 28% of females had less than 1mm of the discrepancy of F1 midline to maxillary midline whereas 41% of males and 38% of females had less than 1 mm of a discrepancy between F2 facial midline and maxillary midline. The study also showed that 24% of males and 24.66% of females had none coincidence of any of the midlines with one another. Conclusion: Most of the Nepalese have noncoinciding facial and dental midline but females have more coinciding midlines in comparison to males. The shifted facial midlines are more towards the left side in relation to maxillary dental midline.