Jaw Development Research Articles

Investigation of the force reactions’ magnitude around the mounts of orthodontic appliances in the process of orthodontic treatment of children with congenital unilateral cleft lip and palate

For the purpose of orthodontic treatment of children with congenital cleft lip and palate, various orthodontic constructions are used. The use of removable appliances indicated for narrowing or shortening of the dental arches, anomalies of the individual teeth position. The question of determining the magnitude of force reactions around special devices (clasps) that are designed to fix appliances on teeth during treatment, under the conditions of the specificity of the development of the upper jaw and the impact of surgical interventions on it, requires detailing, which determined the purpose of this research. A three-dimensional 3D simulation model was created based on digital data of the spatial geometry of a sample of orthodontic appliance used for orthodontic treatment of children with congenital unilateral cleft lip and palate. Mathematical modeling methods were used to study the stress-deformed state of the appliance and estimate the magnitudes and distribution of the amplitudes of force reactions around its fasteners (clasps). Force reactions around of the supports of the orthodontic appliance when the screw is rotated from 0° to 360° (axial movement by 1 mm) are unevenly distributed, with a minimum value of force amplitudes of 10.3 N and a maximum of 30.9 N. It was noted that in the area of fasteners (clasps) placed more distally, the values are higher (30.9 N and 27.6 N) than in the medially placed fasteners (10.3 N and 12.5 N). It is also worth noting that on the side of the base of the appliance, which corresponds to the location of the small fragment of the jaw, the values of the force amplitudes are greater (30.9 N and 12.5 N) than on the side of the large fragment (27.6 N and 10.3 N). A significant dependence of the values of force reactions on the stiffness characteristics of the jaw and the type of force transmission from the orthodontic appliance to its areas was established. Keywords: 3D simulation model, force reactions, clasps.

Emergency Treatment of Soft Tissue and Dentoalveolar Fractures using Risdon Wiring in Children due to Motorcycle Accident : Case Report

Introduction: Dentoalveolar fractures are often found in children due to physical trauma, falls, and motorized accidents. In pediatric patients, there are variations in age, jaw development, and dentition which are the primary considerations in choosing a dentoalveolar fracture treatment method. This case report aims to describe and discuss the emergency management of soft tissue injuries and mandibular dentoalveolar fractures with Risdon wiring in pediatric patients due to motorized accidents. Case report: A 9-year-old female patient complained of bleeding from the mouth due to a traffic accident. Clinical and radiographic examination showed dentoalveolar segment fractures in tooth region 32-42, stab wounds, and lacerations on the inferior lip, vestibule, and gingiva in tooth region 32-42. The patient underwent wound cleaning, wound suturing, and treatment of dentoalveolar fractures with fixation using Risdon wiring in the mandibular region 36-46. Conclusion: Conservative treatment of dentoalveolar fractures in pediatric patients with minimal intervention can give good results. Risdon wiring as a fixation method can be used in the emergency treatment of dentoalveolar fractures in pediatric patients with mixed dentition. Keywords: Soft tissue trauma, dentoalveolar fracture, Risdon wiring, emergency

Phylogenetics and the Cenozoic radiation of lampreys

The development of a movable jaw is one of the most important transitions in the evolutionary history of animals.1 Jawed vertebrates rapidly diversified after appearing approximately 470 million years ago. Today, only lampreys and hagfishes represent the once dominant jawless grade2,3,4 and comprise less than 1% of living vertebrate species. Their relationship to other vertebrates ranks among the more contentious problems in animal phylogenetics.5,6,7,8,9,10,11,12 Further, the phylogenetic relationships within lampreys and hagfishes remain unclear,13,14,15 and the ages of their living lineages are largely unexplored.16,17 Because of their importance for the genomic and developmental changes that prefigured jawed vertebrate diversity,18,19,20,21 the evolutionary history of lampreys and hagfishes is a major frontier of organismal biology. Of these two clades, lampreys22 are more ecologically diverse, exhibiting freshwater, anadromous, and fully marine forms, as well as parasitic and nonparasitic species.23,24 Here, we present a new phylogeny and historical biogeographic reconstruction of all living lampreys. Whereas the early diversification of this clade tracks Pangaean fragmentation, lampreys also rapidly radiated in the northern hemisphere during the mid-Cretaceous and directly after the Cretaceous-Paleogene extinction. These radiations mirrored concurrent ones in other animals and plants and coincided with changes to lamprey ecology and feeding behavior. Our results suggest that 80% of living lamprey clades appeared in the last 20 million years of Earth history. Rather than gradually accumulating since the oldest stem-group forms appeared in the early Paleozoic, living lamprey biodiversity results from diversifications extending from the Cretaceous to present.

In utero exposure to selective serotonin re-uptake inhibitor affects murine mandibular development.

Antidepressants, specifically Selective Serotonin Re-uptake Inhibitors (SSRIs), that alter serotonin metabolism are currently the most commonly prescribed drugs for the treatment of depression. There is some evidence to suggest these drugs contribute to birth defects. As jaw development is often altered in craniofacial birth defects, the purpose of this study was to interrogate the effects of in utero SSRI exposure in a preclinical model of mandible development. Wild-type C57BL6 mice were used to produce litters that were exposed in utero to an SSRI, Citalopram (500 μg/day). Murine mandibles from P15 pups were analysed for a change in shape and composition. Analysis indicated an overall shape change with total mandibular length and ramus height being shorter in exposed pups as compared to controls. Histomorphometric analysis revealed that first molar length was longer in exposed pups while third molar length was shorter in exposed as compared to control. Histological investigation of molars and surrounding periodontium revealed no change in collagen content of the molar in exposed pups, some alteration in collagen composition in the periodontium, increased alkaline phosphatase in molars and periodontium and decreased mesenchymal cell marker presence in exposed mandibles. The results of this study reveal SSRI exposure may interrupt mandible growth as well as overall dental maturation in a model of development giving insight into the expectation that children exposed to SSRIs may require orthodontic intervention.

Novel Genetic Determinants of Dental Maturation in Children

Dental occlusion requires harmonious development of teeth, jaws, and other elements of the craniofacial complex, which are regulated by environmental and genetic factors. We performed the first genome-wide association study (GWAS) on dental development (DD) using the Demirjian radiographic method. Radiographic assessments from participants of the Generation R Study (primary study population, N1 = 2,793; mean age of 9.8 y) were correlated with ~30 million genetic variants while adjusting for age, sex, and genomic principal components (proxy for population stratification). Variants associated with DD at genome-wide significant level (P < 5 × 10−8) mapped to 16q12.2 (IRX5) (lead variant rs3922616, B = 0.16; P = 2.2 × 10−8). We used Fisher’s combined probability tests weighted by sample size to perform a meta-analysis (N = 14,805) combining radiographic DD at a mean age of 9.8 y from Generation R with data from a previous GWAS (N2 = 12,012) on number of teeth (NT) in infants used as proxy of DD at a mean age of 9.8 y (including the ALSPAC and NFBC1966). This GWAS meta-analysis revealed 3 novel loci mapping to 7p15.3 (IGF2BP3: P = 3.2 × 10−8), 14q13.3 (PAX9: P = 1.9 × 10−8), and 16q12.2 (IRX5: P = 1.2 × 10−9) and validated 8 previously reported NT loci. A polygenic allele score constructed from these 11 loci was associated with radiographic DD in an independent Generation R set of children (N = 703; B = 0.05, P = 0.004). Furthermore, profiling of the identified genes across an atlas of murine and human stem cells observed expression in the cells involved in the formation of bone and/or dental tissues (>0.3 frequency per kilobase of transcript per million mapped reads), likely reflecting functional specialization. Our findings provide biological insight into the polygenic architecture of the pediatric dental maturation process.

The insufficiency of Dlx5 for ventral patterning in post-migratory neural crest cells reveals a loss of plasticity in early jaw-forming tissue

The articulated jaws of vertebrates arise from the first pharyngeal arch, the most rostral of several transient ventral structures in pharyngeal stage embryos. Migratory cranial neural crest cells from the caudal midbrain and rostral hindbrain populate the first arch as ectomesenchyme and supply the progenitors of skeletal and soft tissues that form the upper (maxillary) and lower (mandibular) jaws. Dlx genes encode key transcriptional regulators that profoundly influence jaw development through their actions in first pharyngeal arch patterning. The broadly conserved nested expression of Dlx paralogues in vertebrate embryos points to a retained ancestral role in patterning first arch tissue. Loss-of-function experiments consistently highlight the necessity of Dlx gene function for jaw morphogenesis. Specifically, the combined effects of Dlx5 and Dlx6 are required to specify ventral/mandibular fate and forced expression of Dlx5 in migrating neural crest cells results in the ectopic upregulation of ventral markers in the maxillary arch. Here, we ask whether Dlx5 is also sufficient to respecify post-migratory ectomesenchyme in the maxillary branch as mandibular. Unexpectedly, we show that Dlx5 is not sufficient to activate mandibular marker genes in the maxillary branch of PA1, highlighting a loss of plasticity in post-migratory first arch ectomesenchyme.

A Survey Study on Sleep Breathing in Individuals with Malocclusion Characterized by Maxillary Transversal Deficiency and Snoring Problem

Aim: The aim of this survey study is to evaluate the awareness of parents on sleep disorders and their side effects, and to measure their level of awareness to those respiratory problems can lead to dental and jaw disorders. &#x0D; Materials and Methods: A survey was applied to the parents of 30 children whose average age was 11.86, who had snoring, mouth breathing, and narrow maxilla, who applied to the Department of Orthodontics, Faculty of Dentistry, Ankara University. While the first six questions of the questionnaire are about general information, the next 37 questions are about the smoking status of the parents, the child's snoring characteristics, and apnea, day and night complaints that are typically seen in children with Obstructive Sleep Apnea Syndrome. &#x0D; Result: In our survey study, it was determined that the awareness of people that snoring in children can be a symptom of a disease is weak. 40% of parents do not have information on this issue. In addition to that, parents do not think that snoring seen in children while sleeping at night may influence school success. &#x0D; Conclusion: In our study, it was found that the level of awareness of parents about the effects of breathing problems during sleep on jaw development was also low. Because of that, orthodontists and physicians interested in sleep should inform the society more about this issue.

The expression and significance of vascular endothelial growth factor A in adenoid cystic carcinoma of palatal salivary gland.

To explore the VEGF-A expression in salivary gland adenoid cystic carcinoma tissues and detect the relationship between the mechanism of occurrence, development and metastasis of jaws with salivary gland adenoid cystic carcinoma and VEGF-A expression. Paraffin samples from 58 cases of SACC of the palate and ten cases of normal salivary gland tissues were collected. The expression levels of VEGF-A protein were detected using the immunohistochemistry EnVision system. Among the 58 cases, there were 20 cases of the cribriform type, 17 cases of the tubular type, and 21 cases of the solid type. There were 9 cases with lymph node metastasis and 21 cases without lymph node metastasis. And there were 8 cases of T1, 15 cases of T2, and 7 cases of T3/T4. The positive expression rate of VEGF-A in SACC of the palate was 74.1%, which was higher than that found in normal salivary gland tissues (10%). The VEGF-A was localized in the cytoplasm/cell membrane. VEGF-A is highly expressed in SACC of the palate. The level of expression is closely related to the pathological grade, lymph node metastasis, and clinical stage of the tumor, and it can thus be used as an important indicator for judging the biological behavior of SACC of the palate.

Fgf8 dosage regulates jaw shape and symmetry through pharyngeal-cardiac tissue relationships.

Asymmetries in craniofacial anomalies are commonly observed. In the facial skeleton, the left side is more commonly and/or severely affected than the right. Such asymmetries complicate treatment options. Mechanisms underlying variation in disease severity between individuals as well as within individuals (asymmetries) are still relatively unknown. Developmental reductions in fibroblast growth factor 8 (Fgf8) have a dosage dependent effect on jaw size, shape, and symmetry. Further, Fgf8 mutants have directionally asymmetric jaws with the left side being more affected than the right. Defects in lower jaw development begin with disruption to Meckel's cartilage, which is discontinuous. All skeletal elements associated with the proximal condensation are dysmorphic, exemplified by a malformed and misoriented malleus. At later stages, Fgf8 mutants exhibit syngnathia, which falls into two broad categories: bony fusion of the maxillary and mandibular alveolar ridges and zygomatico-mandibular fusion. All of these morphological defects exhibit both inter- and intra-specimen variation. We hypothesize that these asymmetries are linked to heart development resulting in higher levels of Fgf8 on the right side of the face, which may buffer the right side to developmental perturbations. This mouse model may facilitate future investigations of mechanisms underlying human syngnathia and facial asymmetry.

Species-specific sensitivity to TGFβ signaling and changes to the Mmp13 promoter underlie avian jaw development and evolution.

Precise developmental control of jaw length is critical for survival, but underlying molecular mechanisms remain poorly understood. The jaw skeleton arises from neural crest mesenchyme (NCM), and we previously demonstrated that these progenitor cells express more bone-resorbing enzymes including Matrix metalloproteinase 13 (Mmp13) when they generate shorter jaws in quail embryos versus longer jaws in duck. Moreover, if we inhibit bone resorption or Mmp13, we can increase jaw length. In the current study, we uncover mechanisms establishing species-specific levels of Mmp13 and bone resorption. Quail show greater activation of and sensitivity to transforming growth factor beta (TGFβ) signaling than duck; where intracellular mediators like SMADs and targets like Runt-related transcription factor 2 (Runx2), which bind Mmp13, become elevated. Inhibiting TGFβ signaling decreases bone resorption, and overexpressing Mmp13 in NCM shortens the duck lower jaw. To elucidate the basis for this differential regulation, we examine the Mmp13 promoter. We discover a SMAD-binding element and single nucleotide polymorphisms (SNPs) near a RUNX2-binding element that distinguish quail from duck. Altering the SMAD site and switching the SNPs abolish TGFβ sensitivity in the quail Mmp13 promoter but make the duck promoter responsive. Thus, differential regulation of TGFβ signaling and Mmp13 promoter structure underlie avian jaw development and evolution.

Meckel’s Cartilage in Mandibular Development and Dysmorphogenesis

The Fgfr2c C342Y/+ Crouzon syndrome mouse model carries a cysteine to tyrosine substitution at amino acid position 342 (Cys342Tyr; C342Y) in the fibroblast growth factor receptor 2 (Fgfr2) gene equivalent to a FGFR2 mutation commonly associated with Crouzon and Pfeiffer syndromes in humans. The Fgfr2c C342Y mutation results in constitutive activation of the receptor and is associated with upregulation of osteogenic differentiation. Fgfr2cC342Y/+ Crouzon syndrome mice show premature closure of the coronal suture and other craniofacial anomalies including malocclusion of teeth, most likely due to abnormal craniofacial form. Malformation of the mandible can precipitate a plethora of complications including disrupting development of the upper jaw and palate, impediment of the airway, and alteration of occlusion necessary for proper mastication. The current paradigm of mandibular development assumes that Meckel’s cartilage (MC) serves as a support or model for mandibular bone formation and as a template for the later forming mandible. If valid, this implies a functional relationship between MC and the forming mandible, so mandibular dysmorphogenesis might be discerned in MC affecting the relationship between MC and mandibular bone. Here we investigate the relationship of MC to mandible development from the early mineralization of the mandible (E13.5) through the initiation of MC degradation at E17.7 using Fgfr2c C342Y/+ Crouzon syndrome embryos and their unaffected littermates (Fgfr2c +/+ ). Differences between genotypes in both MC and mandibular bone are subtle, however MC of Fgfr2c C342Y/+ embryos is generally longer relative to unaffected littermates at E15.5 with specific aspects remaining relatively large at E17.5. In contrast, mandibular bone is smaller overall in Fgfr2c C342Y/+ embryos relative to their unaffected littermates at E15.5 with the posterior aspect remaining relatively small at E17.5. At a cellular level, differences are identified between genotypes early (E13.5) followed by reduced proliferation in MC (E15.5) and in the forming mandible (E17.5) in Fgfr2c C342Y/+ embryos. Activation of the ERK pathways is reduced in the perichondrium of MC in Fgfr2c C342Y/+ embryos and increased in bone related cells at E15.5. These data reveal that the Fgfr2c C342Y mutation differentially affects cells by type, location, and developmental age indicating a complex set of changes in the cells that make up the lower jaw.

Meckel’s Cartilage and Mandibles: Effects of the Fgfr2 C342Y mutation on development of the lower jaw in a Crouzon syndrome mouse model

The Fgfr2cC342Y/+ Crouzon syndrome mouse model carries a cysteine to tyrosine substitution at amino acid position 342 (Cys342Tyr; C342Y) in fibroblast growth factor receptor 2 (FGFR2), equivalent to the FGFR2 mutation commonly associated with Crouzon syndrome. Crouzon syndrome is an autosomal dominant condition characterized by craniofacial anomalies. The FGFR2 C342Y mutation results in constitutive activation of the receptor and is associated with up‐regulation of osteogenic differentiation. Although premature closure of the coronal suture is the focus of most studies of Crouzon syndrome, cartilage elements of the skull are also known to be affected by this mutation. Fgfr2cC342Y/+ Crouzon syndrome mice commonly exhibit malocclusion of the jaws, most likely due to abnormal craniofacial form. The current paradigm of mandibular development assumes Meckel’s cartilage (MC) provides a model for mandibular development. Malformation of the mandible can precipitate a plethora of complications including disrupting development of the upper jaw and the palate, impediment of the airway, as well as altering the functional occlusion necessary for proper mastication. Here we investigate the relationship of Meckel’s cartilage to mandible development. Using Fgfr2cC342Y/+ Crouzon syndrome mice and their unaffected littermates (Fgfr2c+/+ mice) at embryonic days 15.5 and 17.5 we explore the form of Meckel’s cartilage and the developing mandible as Meckel’s cartilage begins to degrade. A histological assessment of the chondrocytes within Meckel’s cartilage reveals few differences in cell size between genotypes at either timepoint, however there are more chondrocytes present in the most anterior aspects of the cartilage in Fgfr2cC342Y/+ mice at E15.5. No differences between genotypes were found in osteoblast (ALP) or osteoclast (TRAP) activity of the mandibles at E15.5 but osteoclast activity was greater in unaffected Fgfr2c+/+ mice at E17.5. These data reveal that further investigation of Crouzon syndrome mice can uncover differential effects of the C342Y mutation in FGFR2 in cells other than those surrounding the coronal suture.

NOVEL APPROACHES IN BREAKING ORAL HABITS IN CHILDREN

Aim: Oral habits are harmful to one's health due to their propensity to alter the dentoskeletal as well as musculoskeletal development of jaws. The purpose of this study was to systematically review the newer treatment modalities being used by the clinicians to interrupt the habit and their detrimental consequences on the child’s oral well-being. Materials and Methods: A total of 46 articles were screened, with 40 articles being excluded, 5 full-text articles being evaluated for eligibility to be reviewed for the present paper. Conclusion: Newer approaches for cessation of oral habits show better compliance and are more cost effective than the conventional one

Ulcerated White Lesion of Tongue in a 7-Year-Old Child: A Diagnostic Dilemma

Tongue is a complex organ associated with functions of taste, speech, mastication, deglutition, and development of jaws. It is considered the mirror of physical health as it can be the site of infections, immunological and drug-induced reactions, neoplasms and systemic diseases. This paper aims to present challenges in diagnosing a case of a 7-year-old male child who presented with ulceration and extensive white coating on the dorsum of tongue accompanied by fever, chills, tonsillitis, and submandibular lymphadenopathy. Despite symptomatic treatment done, the white coating with patches of depapillation lasted for a relatively long time. This may be the first reported case in the literature with such unusual tongue lesions in a child till date. Thus, pediatric dentists should have sound knowledge of the commonly encountered oral soft tissue lesions along with the rarer lesions and unusual presentation of common lesions for timely diagnosis, appropriate treatment, and referral if necessary.

Involvement of homeobox transcription factor Mohawk in palatogenesis.

Palatogenesis is affected by many factors, including gene polymorphisms and exposure to toxic chemicals during sensitive developmental periods. Cleft palate is one of the most common congenital anomalies, and ongoing efforts to elucidate the molecular mechanisms underlying palatogenesis are providing useful insights to reduce the risk of this disorder. To identify novel potential regulators of palatogenesis, we analyzed public transcriptome datasets from a mouse model of cleft palate caused by selective deletion of transforming growth factor-β (TGFβ) receptor type 2 in cranial neural crest cells. We identified the homeobox transcription factor Mohawk (Mkx) as a gene downregulated in the maxilla of TGFβ knockout mice compared with wild-type mice. To examine the role of mkx in palatogenesis, we used CRISPR/Cas9 editing to generate zebrafish with impaired expression of mkxa and mkxb, the zebrafish homologs of Mkx. We found that mkx crispants expressed reduced levels of gli1, a critical transcription factor in the Sonic hedgehog (SHH) signaling pathway that plays an important role in the regulation of palatogenesis. Furthermore, we found that mkxa-/- zebrafish were more susceptible than mkxa+/+ zebrafish to the deleterious effects of cyclopamine, an inhibitor of SHH signaling, on upper jaw development. These results suggest that Mkx may be involved in palatogenesis regulated by TGFβ and SHH signaling, and that impairment in Mkx function may be related to the etiology of cleft palate.

Prevalence of Occlusal Features and Their Relation to Sociodemographic Variables in Northwest Ethiopia: A Cross-Sectional Study.

BackgroundMalocclusion affects the chewing, dental aesthetics, jaw development, and overall attractiveness of individuals. The negative impact of malocclusion is high, particularly in adolescents who can be the target of teasing, intimidation, and name-calling. Even if, malocclusion is a common problem in developing countries, there was a paucity of data in Ethiopia. Therefore, this study aimed to determine the prevalence and associated factors of malocclusion in northwest Ethiopia.MethodsThis cross-sectional study was done at the University of Gondar comprehensive hospital from December 1, 2019, to October 30, 2020. Four hundred seventy-six study participants were selected using a systematic random sampling method. Data collection was done using a structured interviewer-administered questionnaire. Qualified dental professionals examined malocclusion traits according to the WHO oral health survey tool and evaluated for the presence of malocclusion in terms of angles classification, open bite, crossbite, spacing, and crowding. Data entry was done using Epi-Info 7, and analyzed by SPSS 26. Descriptive statistics and logistic regression was done to analyze the data.ResultsA total of 476 subjects were included in the study with a mean age of 29.83 (SD±14.013). The prevalence of malocclusion was 55.9% (95% CI: 51.39–60.28). The common occlusal traits were class-I malocclusion with minor discrepancy (34.9%), anterior crowding (22.9%), and anterior open bite (21.6%). The prevalence of anterior crossbite, posterior crossbite, class-II, and class-III malocclusion was 5.9%, 3.8%, 10.9%, and 8.0%, respectively. Males (AOR=1.6, 95% CI: 1.11, 2.30), urban residents (AOR=1.64, 95% CI: 1.06, 2.56), monthly income of ≤2500 Ethiopian Birr (AOR=1.27, 95% CI: 1.02, 1.59) and mouth breathers (AOR=2.50, 95% CI: 1.72, 2.63) were significantly associated with malocclusion.ConclusionSignificant amount of the study participants had malocclusion. Males, urban residents, low monthly income, and mouth breathing habits were independent factors for a malocclusion. Therefore, early attention to the development of the dentition and occlusion, and necessary functional correction during childhood are important to reduce its prevalence and lifelong adverse effect. Moreover, publicly financed orthodontic treatment should be scheduled, and supplied to individuals in desperate need of orthodontic care.

Finding Their Own Way: Bilateral Ectopic Premolar Teeth that Spontaneously Repositioned during a Course of Jaw Development Orthodontic Therapy: A Case Report and Literature Review

Finding Their Own Way: Bilateral Ectopic Premolar Teeth that Spontaneously Repositioned during a Course of Jaw Development Orthodontic Therapy: A Case Report and Literature Review

Long-term follow-up after arthroplasty for pediatric temporomandibular joint ankylosis performed before the critical period of mandibular growth: A case report.

Introduction and importancePediatric temporomandibular joint (TMJ) ankylosis can lead to significant difficulties in opening the mouth, as well as stunted mandibular growth resulting in a small mandible and facial asymmetry. For pediatric TMJ ankylosis, the ideal time to perform TMJ mobilization in order to achieve standard mandibular growth is unclear.Case presentationAn 11-year-old boy with limited mouth opening was referred to our hospital. The patient had previously sustained a fracture of the left articular process of the mandible. Clinical examination revealed bony ankylosis of the left TMJ, and the condylar head was dislocated anteromedially. The bony ankylosis was removed at the age of 12 years. Mouth-opening exercises were started postoperatively. His mouth opening recovered without the development of severe facial asymmetry, and the dislocated condylar process served as a new joint and provided good jaw function until the most recent follow-up at the age of 21 years.Clinical discussionIt is practical to perform surgical intervention after the child has achieved some growth and at a time when the surgery would not interfere with jaw development because the mouth opening can be improved by postoperative physical therapy. No interpositional implant was used because strict postoperative mouth opening exercises and the displaced condylar process, which was maintained to almost normal TMJ structure, were expected to preserve the gap between the ramus and the zygomatic arch.ConclusionSurgical intervention in the appropriate growth period is important to prevent the sequelae of mandibular growth suppression due to pediatric TMJ ankylosis.

A show of Hands: Novel and conserved expression patterns of teleost hand paralogs during craniofacial, heart, fin, peripheral nervous system and gut development.

Hand genes are required for the development of the vertebrate jaw, heart, peripheral nervous system, limb, gut, placenta, and decidua. Two Hand paralogues, Hand1 and Hand2, are present in most vertebrates, where they mediate different functions yet overlap in expression. In ray-finned fishes, Hand gene expression and function is only known for the zebrafish, which represents the rare condition of having a single Hand gene, hand2. Here we describe the developmental expression of hand1 and hand2 in the cichlid Copadichromis azureus. hand1 and hand2 are expressed in the cichlid heart, paired fins, pharyngeal arches, peripheral nervous system, gut, and lateral plate mesoderm with different degrees of overlap. Hand gene expression in the gut, peripheral nervous system, and pharyngeal arches may have already been fixed in the lobe- and ray-finned fish common ancestor. In other embryonic regions, such as paired appendages, hand2 expression was fixed, while hand1 expression diverged in lobe- and ray-finned fish lineages. In the lateral plate mesoderm and arch associated catecholaminergic cells, hand1 and hand2 swapped expression between divergent lineages. Distinct expression of cichlid hand1 and hand2 in the epicardium and myocardium of the developing heart may represent the ancestral pattern for bony fishes.

A Systems-Based Key Innovation-Driven Approach Infers Co-option of Jaw Developmental Programs During Cancer Progression.

Cancer acquires metastatic potential and evolves via co-opting gene regulatory networks (GRN) of embryonic development and tissue homeostasis. Such GRNs are encoded in the genome and frequently conserved among species. Considering that all metazoa have evolved from a common ancestor via major macroevolutionary events which shaped those GRNs and increased morphogenetic complexity, we sought to examine whether there are any key innovations that may be consistently and deterministically linked with metastatic potential across the metazoa clades. To address tumor evolution relative to organismal evolution, we revisited and retrospectively juxtaposed seminal laboratory and field cancer studies across taxa that lie on the evolutionary lineage from cnidaria to humans. We subsequently applied bioinformatics to integrate species-specific cancer phenotypes, multiomics data from up to 42 human cancer types, developmental phenotypes of knockout mice, and molecular phylogenetics. We found that the phenotypic manifestations of metastasis appear to coincide with agnatha-to-gnathostome transition. Genes indispensable for jaw development, a key innovation of gnathostomes, undergo mutations or methylation alterations, are aberrantly transcribed during tumor progression and are causatively associated with invasion and metastasis. There is a preference for deregulation of gnathostome-specific versus pre-gnathostome genes occupying hubs of the jaw development network. According to these data, we propose our systems-based model as an in silico tool the prediction of likely tumor evolutionary trajectories and therapeutic targets for metastasis prevention, on the rationale that the same genes which are essential for key innovations that catalyzed vertebrate evolution, such as jaws, are also important for tumor evolution.