Inactivation of Zeb1 in GRHL2-deficient mouse embryos rescues mid-gestation viability and secondary palate closure.

Cleft lip and palate are common birth defects resulting from failure of the facial processes to fuse during development. The mammalian grainyhead-like (Grhl1-3) genes play key roles in a number of tissue fusion processes including neurulation, epidermal wound healing and eyelid fusion. One family member, Grhl2, is expressed in the epithelial lining of the first pharyngeal arch in mice at embryonic day (E)10.5, prompting analysis of the role of this factor in palatogenesis. Grhl2-null mice die at E11.5 with neural tube defects and a cleft face phenotype, precluding analysis of palatal fusion at a later stage of development. However, in the first pharyngeal arch of Grhl2-null embryos, dysregulation of transcription factors that drive epithelial-mesenchymal transition (EMT) occurs. The aberrant expression of these genes is associated with a shift in RNA-splicing patterns that favours the generation of mesenchymal isoforms of numerous regulators. Driving the EMT perturbation is loss of expression of the EMT-suppressing transcription factors Ovol1 and Ovol2, which are direct GRHL2 targets. The expression of the miR-200 family of microRNAs, also GRHL2 targets, is similarly reduced, resulting in a 56-fold upregulation of Zeb1 expression, a major driver of mesenchymal cellular identity. The critical role of GRHL2 in mediating cleft palate in Zeb1-/- mice is evident, with rescue of both palatal and facial fusion seen in Grhl2-/-;Zeb1-/- embryos. These findings highlight the delicate balance between GRHL2/ZEB1 and epithelial/mesenchymal cellular identity that is essential for normal closure of the palate and face. Perturbation of this pathway may underlie cleft palate in some patients.

Jaws can be referred to as narrow or hypoplastic, but the term "atresia" is inaccurate!

ABSTRACT In order to lead to insights and discussion on proper use of Orthodontics and Pathology-related terminology, particularly in cases of smaller-than-usual maxilla and mandible - that is, anomalous ones -, this study compared the conceptual meaning of the term "atresia." It is considered improper when referring to maxilla and mandible with deficient growth compared to development that is satisfactory enough to reach normal size. To identify smaller maxilla and mandible, the most proper and accurate term is hypoplastic maxilla or mandible. This is because "atresia" stands for an anomaly related to lumen blockage in hollow organs, which is not the case for neither maxilla nor mandible. Hypoplastic maxilla or mandible can be properly and specifically referred to as micrognathia.

RESUMO Para induzir reflexões e discussões sobre o uso adequado da nomenclatura em Ortodontia e Patologia, para os casos em que a maxila e a mandíbula apresentam-se pequenas ou menores do que o habitual, ou seja, anômalas, comparou-se o significado conceitual do termo "atrésica". Esse termo não é adequado quando aplicado à maxila e à mandíbula para identificar situações em que houve um desenvolvimento com crescimento insuficiente para se chegar ao tamanho normal. Para identificar maxila e mandíbula menores, é mais adequado e preciso o uso do termo maxila ou mandíbula hipoplásica. Isso porque atresia representa uma anomalia por obstrução da luz ou lume em órgãos ocos, o que não ocorre na maxila ou na mandíbula. Maxila ou mandíbula hipoplásica também podem ser chamadas, apropriada e especificamente, de micrognatia.

[Diagnostic and therapeutic interest of studying the nose in maxillo-dento-facial orthopedics]. / Intérêt diagnostique et thérapeutique de l'étude du nez en orthopédie dento-maxillo-faciale.

INTRODUCTION: Orthodontists have long tried to predict future growth. It is one of the most difficult goals to achieve precisely despite the different methods of growth forecasting. A simple technique based on clinical and radiological analyses of the nose and premaxilla makes it possible, using no measurements, to accurately predict future maxillary growth and to deduce the therapeutic indications. A morphologic study of the nose is also an important item in the diagnosis of cranio-facial syndromes. MATERIALS AND METHODS: Combining detailed semiologic and radiologic studies of the nasal and premaxillary structures, this article proposes a method for evaluating and predicting facial growth. RESULTS: Experience based on many observations and current embryological knowledg can detect growth abnormalities of the ethmoïdo-nasal-premaxillary unit and provide valuable therapeutic information. DISCUSSION: Combining clinical and radiologic analyses of nasal and premaxillary morphology is a good method to predict growth of the upper face. It is also an important feature in the diagnosis of cranio-facial syndromes. CONCLUSION: This technique should be included in the diagnosis of maxillo-dento-facial orthopedic cases.

Foxf2 is required for secondary palate development and Tgfß signaling in palatal shelf mesenchyme.

The secondary palate separates the oral from the nasal cavity and its closure during embryonic development is sensitive to genetic perturbations. Mice with deleted Foxf2, encoding a forkhead transcription factor, are born with cleft palate, and an abnormal tongue morphology has been proposed as the underlying cause. Here, we show that Foxf2(-/-) maxillary explants cultured in vitro, in the absence of tongue and mandible, failed to close the secondary palate. Proliferation and collagen content were decreased in Foxf2(-/-) palatal shelf mesenchyme. Phosphorylation of Smad2/3 was reduced in mutant palatal shelf, diagnostic of attenuated canonical Tgfß signaling, whereas phosphorylation of p38 was increased. The amount of Tgfß2 protein was diminished, whereas the Tgfb2 mRNA level was unaltered. Expression of several genes encoding extracellular proteins important for Tgfß signaling were reduced in Foxf2(-)(/)(-) palatal shelves: a fibronectin splice-isoform essential for formation of extracellular Tgfß latency complexes; Tgfbr3 - or betaglycan - which acts as a co-receptor and an extracellular reservoir of Tgfß; and integrins αV and ß1, which are both Tgfß targets and required for activation of latent Tgfß. Decreased proliferation and reduced extracellular matrix content are consistent with diminished Tgfß signaling. We therefore propose that gene expression changes in palatal shelf mesenchyme that lead to reduced Tgfß signaling contribute to cleft palate in Foxf2(-)(/)(-) mice.

Biologic characteristics and osteogenic differentiation of maxillary primordium mesenchymal cells.

OBJECTIVE: The aim of this study was to investigate the biologic characteristics and osteogenic differentiation of mouse maxillary primordium mesenchymal cells (MPMCs) in vitro. METHODS: The MPMCs were obtained from the E13.5 mouse embryos and cultured in vitro. The biologic characteristics were studied based on general observation and 5-Bromo-2-deoxyUridine (BrdU) label. The MPMCs from the first passage were cultured in the osteogenic medium for 1 week. Then, the immunofluorescence staining, alkaline phosphatase staining, Alizarin red S staining, and quantity polymerase chain reaction were used to evaluate the osteogenic capability of MPMCs. RESULTS: The E13.5 MPMCs were successfully adherent cultured and passaged in vitro. These cells expressed Dlx2 and SMAD7, two genes that play important roles in the development of maxillary primordium. The percentage of 5-Bromo-2-deoxyUridine-labeled MPMCs was 32.1%. Osteogenic induction could promote the expression of Runx2, osteocalcin, and osteopontin, 3 osteogenic markers, in MPMCs. In addition, osteogenic induction could stimulate the secretion of alkaline phosphatase and promote the deposition of calcium nodules in MPMCs. CONCLUSIONS: The MPMCs could be cultured in vitro and could differentiate into osteoblast in vitro through osteogenic induction. It offered an alternative cell source to regenerate craniofacial bone and offered a useful cell model to study the craniofacial bone development.

Directed Bmp4 expression in neural crest cells generates a genetic model for the rare human bony syngnathia birth defect.

Congenital bony syngnathia, a rare but severe human birth defect, is characterized by bony fusion of the mandible to the maxilla. However, the genetic mechanisms underlying this birth defect are poorly understood, largely due to limitation of available animal models. Here we present evidence that transgenic expression of Bmp4 in neural crest cells causes a series of craniofacial malformations in mice, including a bony fusion between the maxilla and hypoplastic mandible, resembling the bony syngnathia syndrome in humans. In addition, the anterior portion of the palatal shelves emerged from the mandibular arch instead of the maxilla in the mutants. Gene expression assays showed an altered expression of several facial patterning genes, including Hand2, Dlx2, Msx1, Barx1, Foxc2 and Fgf8, in the maxillary and mandibular processes of the mutants, indicating mis-patterned cranial neural crest (CNC) derived cells in the facial region. However, despite of formation of cleft palate and ectopic cartilage, forced expression of a constitutively active form of BMP receptor-Ia (caBmprIa) in CNC lineage did not produce the syngnathia phenotype, suggesting a non-cell autonomous effect of the augmented BMP4 signaling. Our studies demonstrate that aberrant BMP4-mediated signaling in CNC cells leads to mis-patterned facial skeleton and congenital bony syngnathia, and suggest an implication of mutations in BMP signaling pathway in human bony syngnathia.

Magnetic resonance imaging evaluation of fetal maxillary sinuses.

BACKGROUND AND OBJECTIVE: The growth of maxillary sinus is closely connected to the development of facial structures. However, its definition and reference standards on fetal magnetic resonance imaging (MRI) have not been analyzed so far. In this study, the objectives were to define and evaluate the fetal maxillary sinus (fMS) formation with MRI. METHODS: We reviewed T2-weighted coronal MRI images of 75 fetuses. The MRI features, time of appearance, and boundaries of fMS were defined. Craniocaudal and transverse diameters of both maxillary sinuses and bone biparietal diameters were measured and statistically evaluated. RESULTS: In 150 fMS site analysis, 91 fMSs were identified. The fMSs were visualized as a hyperintense structures on T2-weighted image above the tooth bud. It first appeared at the 22nd gestational week, and in 4% (3/75) of fetuses, there was unilateral development. Mean craniocaudal length was 2.84 mm (1.1-4.8 mm), and mean transverse diameter was 2.67 mm (1.5-4.2 mm). CONCLUSIONS: Magnetic resonance imaging features of fMS that should be sought for the assessment of craniofacial anatomy are identified in this study. Fetal maxillary sinuses can be observed as hyperintense structures on T2-weighted MRI images starting from 22 weeks of gestation. The growth of fMS follows a predictable course throughout gestation; however, the dimensions are larger than the previously reported ex vivo series.

Wnt16 is involved in intramembranous ossification and suppresses osteoblast differentiation through the Wnt/ß-catenin pathway.

In the course of embryonic development skeletal elements form either through intramembranous or endochondral ossification. Wnt proteins play diverse roles during vertebrate skeletal development. Wnt16 is a key factor in developing long bones, but its exact role in craniofacial bone formation remains unclear. This study was initially undertaken to investigate the expression of Wnt16 during craniofacial bone development in mouse embryos. Wnt16 expression in the osteoid of calvaria, maxilla, and mandible started later than that of ALP and osteocalcin (OCN), but before mineralization of the craniofacial bones, suggesting that Wnt16 is involved in intramembranous ossification in the head. To confirm this, MC3T3-E1 cells were transfected with an adenovirus containing Wnt16 (Ad-Wnt16). Ad-Wnt16 cells showed decreased ALP activity and less mineralized nodule formations compared with control cells. In addition, the mRNA levels of osteogenic markers were reduced. Moreover, Wnt16 activated ß-catenin signaling in MC3T3-E1 cells at both transcription and protein levels as shown by a TOPflash luciferase reporter gene assay and western blot analysis. On the other hand, Wnt/ß-catenin pathway blockade by Dickkopf 1 abrogated the suppression of mineralization by Wnt16. Our findings suggest that Wnt16 is involved in intramembranous ossification and suppresses osteoblast differentiation through the Wnt/ß-catenin pathway.

Genetic basis for tooth malformations: from mice to men and back again.

Teeth arise from sequential and reciprocal interactions between the oral epithelium and the cranial neural crest-derived mesenchyme. Their formation involves a precisely orchestrated series of molecular and morphogenetic events. Numerous regulatory genes that have been primarily found in organisms such as Drosophila, zebrafish, xenopus and mouse are associated with all stages of tooth formation (patterning, morphogenesis, cytodifferentiation and mineralization). Most of these genes belong to evolutionary conserved signaling pathways that regulate communication between epithelium and mesenchyme during embryonic development. These signaling molecules together with specific transcription factors constitute a unique molecular imprint for odontogenesis and contribute to the generation of teeth with various and function-specific shapes. Mutations in several genes involved in tooth formation cause developmental absence and/or defects of teeth in mice. In humans, the odontogenic molecular program is not as well known as that of mice. However, some insight can be obtained from the study of mutations in regulatory genes, which lead to tooth agenesis and/or the formation of defective dental tissues.

Developmental patterns of Ki-67, bcl-2 and caspase-3 proteins expression in the human upper jaw.

The distribution of the Ki-67, bcl-2 and caspase-3 proteins was immunohistochemically analyzed in the developing human upper jaw (5th-10th gestational weeks). During this period, proliferative activity gradually decreased from higher levels at the earliest stages (50-52%) to lower levels, both in the jaw ectomesenchyme and in the epithelium. The highest expression of bcl-2 protein was found in the epithelium and ectomesenchyme of areas displaying lower rates of cell proliferation. High levels of caspase-3 protein were detected during the earliest stages of jaw development, indicating an important role for apoptosis in morphogenesis of early derivatives of the maxillary prominences. The number of Ki-67, bcl-2 and caspase-3 positive cells changed in a temporally and spatially restricted manner, coincidently with upper jaw differentiation. While apoptosis might control cell number, bcl-2 could act in suppression of apoptosis and enhancement of cell differentiation. A fine balance between cell proliferation (Ki-67), death (caspase-3) and cell survival (bcl-2) characterized early human upper jaw development. A rise in the number of apoptotic cells always temporally coincided with the decrease in number of surviving bcl-2 positive cells within the palatal region. Therefore, the upper jaw development seems to be controlled by the precisely defined expression of genes for proliferation, apoptosis and cell survival.

Maxilla-nasion-mandible angle: a new method to assess profile anomalies in pregnancy.

OBJECTIVES: To collect normative data and test the feasibility and reproducibility of measurement of the maxilla-nasion-mandible (MNM) angle between 16 and 36 weeks' gestation and its diagnostic ability in a group of pathological cases. METHODS: The MNM angle is defined as the angle between the intersection of the maxilla-nasion and mandible-nasion lines in the exact mid-sagittal plane. After assessing reproducibility, the MNM angle was measured in 3D volumes in 241 fetuses cross-sectionally and in 11 fetuses longitudinally. The MNM angle was then tested in 18 pathological cases with facial malformations or syndromes with specific facial features. RESULTS: The MNM angle could be measured in 92.3% of normal fetuses. Intra- and interobserver intraclass correlation coefficient (ICC) variability was 0.92 and 0.81, respectively. The difference between paired measurements performed by one or two observers was less than 2.5° and 3.6°, respectively in 95% of the cases. The mean MNM angle was 13.5° and did not change significantly during pregnancy (r = - 0.08, P = 0.25). The MNM angle was above the 95(th) centile in all cases of retrognathia and maxillary alveolar ridge interruption. The MNM angle was below the 5(th) centile in Apert syndrome, thanatophoric dysplasia and in two of the three Down syndrome cases. CONCLUSIONS: The feasibility and reproducibility of measurement of the MNM angle is good. The MNM angle can be used to evaluate the convexity of the fetal profile by enabling an objective assessment of the anteroposterior relationship of the jaws and it may therefore be of help in the diagnosis of retrognathia, maxillary alveolar ridge interruption and flat profile.

Signaling by FGFR2b controls the regenerative capacity of adult mouse incisors.

Rodent incisors regenerate throughout the lifetime of the animal owing to the presence of epithelial and mesenchymal stem cells in the proximal region of the tooth. Enamel, the hardest component of the tooth, is continuously deposited by stem cell-derived ameloblasts exclusively on the labial, or outer, surface of the tooth. The epithelial stem cells that are the ameloblast progenitors reside in structures called cervical loops at the base of the incisors. Previous studies have suggested that FGF10, acting mainly through fibroblast growth factor receptor 2b (FGFR2b), is crucial for development of the epithelial stem cell population in mouse incisors. To explore the role of FGFR2b signaling during development and adult life, we used an rtTA transactivator/tetracycline promoter approach that allows inducible and reversible attenuation of FGFR2b signaling. Downregulation of FGFR2b signaling during embryonic stages led to abnormal development of the labial cervical loop and of the inner enamel epithelial layer. In addition, postnatal attenuation of signaling resulted in impaired incisor growth, characterized by failure of enamel formation and degradation of the incisors. At a cellular level, these changes were accompanied by decreased proliferation of the transit-amplifying cells that are progenitors of the ameloblasts. Upon release of the signaling blockade, the incisors resumed growth and reformed an enamel layer, demonstrating that survival of the stem cells was not compromised by transient postnatal attenuation of FGFR2b signaling. Taken together, our results demonstrate that FGFR2b signaling regulates both the establishment of the incisor stem cell niches in the embryo and the regenerative capacity of incisors in the adult.

Prenatal sonographic features of fetuses in trisomy 13 pregnancies. IV.

Prenatal ultrasound is a powerful tool to detect structural abnormalities associated with the fetuses in trisomy 13 pregnancies. This article provides a comprehensive review of the prenatal sonographic markers of trisomy 13 in the first trimester, including fetal nuchal translucency thickness, fetal heart rate, fetal nasal bone, fetal tricuspid regurgitation, ductus venous flow, fetal crown-rump length, fetal trunk and head volume, fetal frontomaxillary facial angle, gestational sac volume and umbilical cord diameter, along with biochemical markers such as maternal serum free beta-human chorionic gonadotropin, maternal serum pregnancy-associated plasma protein-A, maternal serum placental growth factor, and the fetal and total cell-free DNA concentration in the maternal circulation.

Arsenate-induced apoptosis in murine embryonic maxillary mesenchymal cells via mitochondrial-mediated oxidative injury.

BACKGROUND: Arsenic is a ubiquitous element that is a potential carcinogen and teratogen and can cause adverse developmental outcomes. Arsenic exerts its toxic effects through the generation of reactive oxygen species (ROS) that include hydrogen peroxide (H(2)O(2)), superoxide-derived hydroxyl ion, and peroxyl radicals. However, the molecular mechanisms by which arsenic induces cytotoxicity in murine embryonic maxillary mesenchymal (MEMM) cells are undefined. METHODS: MEMM cells in culture were treated with different concentrations of pentavalent sodium arsenate [As (V)] for 24 or 48 hr and various end points measured. RESULTS: Treatment of MEMM cells with the pentavalent form of inorganic arsenic resulted in caspase-mediated apoptosis, accompanied by generation of ROS and disruption of mitochondrial membrane potential. Treatment with caspase inhibitors markedly blocked apoptosis. In addition, the free radical scavenger N-acetylcysteine dramatically attenuated arsenic-mediated ROS production and apoptosis, and exposure to arsenate increased Bax and decreased Bcl protein levels in MEMM cells. CONCLUSIONS: Taken together, these findings suggest that in MEMM cells arsenate-mediated oxidative injury acts as an early and upstream initiator of the cell death cascade, triggering cytotoxicity, mitochondrial dysfunction, altered Bcl/Bax protein ratios, and activation of caspase-9.

Tbx22 expressions during palatal development in fetuses with glucocorticoid-/alcohol-induced C57BL/6N cleft palates.

T-box transcription factor 22 (Tbx22) belongs to the T-box family of transcription factors and was originally found using an in silico approach to identify new genes in the human Xq12-Xq21 region. Mutations in Tbx22 have been reported in families with X-linked cleft palate and ankyloglossia, but the underlying pathogenetic mechanism remains unknown. The aim of this study was to evaluate the expression of Tbx22 messenger RNA (mRNA) during palatogenesis in glucocorticoid-/alcohol-induced cleft palate in a C57BL/6N mouse model. Palatal development was monitored by histomorphologic and immunohistochemical studies and by in situ hybridization. Thirty pregnant C57BL/6N mice at 8 weeks of age, weighing 20 to 25 g, were used in this study. In the experimental group, 12 mice were exposed to alcohol for 7 days before mating, and 12 mice in the control group were not exposed. Six mice in a sham group were exposed to neither alcohol nor glucocorticoids. A total of 18 fetuses with induced cleft palates each from 102 fetuses in the experimental group, 109 in the control group, and 58 in the sham group were used. In both the experimental and the control groups, glucocorticoids were injected subcutaneously on gestational days (GD) 9.5, 10.5, and 11.5, and each mouse was killed on GDs 10.5 to 15.5. Histomorphologic findings were studied using hematoxylin and eosin staining, and antibodies against proliferation cell nuclear antigen, matrix metallopeptidase 9, zinc finger protein 422 (Krox25) heat shock protein 70, and Tbx22 were used in immunohistochemical analysis. Mouse Tbx22 mRNA was identified, and its expression was analyzed during embryogenesis by polymerase chain reaction and in situ hybridization. Coronal sections of the cleft maxilla of the embryos with induced cleft palates had a gap between the palatal shelves, where 2 palatal shelves had fused as in normal development but failed to meet and fuse to each other. By in situ hybridization, Tbx22 mRNA was found to be expressed in distinct areas of the head, such as the mesenchyme of the inferior nasal septum, the posterior palatal shelf before fusion, and the attachment of the tongue during normal development of the palate and maxilla from GD 11.5. Localization in the tongue frenum correlated with the ankyloglossia phenotype in the induced cleft palate animal model.

Bilateral variations and sexual dimorphism in morphometric parameters of infraorbital groove, canal and foramen in human foetuses / Variaciones bilaterales y dimorfismo sexual en los parámetros morfométricos del surco, canal y foramen infraorbitario en fetos humanos

Foetal anatomy seems to be highly promising developing speciality in the recent past. Maxilla is the key to facial skeleton. Its anatomy in general and bilateral variations along with sexual dimorphism in particular are of great surgical and forensic importance. Thirty two maxillae of sixteen human foetuses (21 wks to 34 wks) were considered to measure lengths of infraorbital groove and canal, widths of ends of infraorbital groove, diameters of infraorbital foramen and the distances of latter from infraorbital margin and nasal notch. Groups I (21-25 wks) and II (26-30 wks) foetuses were crucial for bilateral variations for most of the parameters. Distance between infraorbital foramen and nasal notch showed variations on two sides in maximum foetal groups. Infraorbital canal was found to be larger in groups II and III foetuses in females. Width of the posterior end of infraorbital groove was less in group I, equal in group II and more in group III in males. Sexual dimorphism was noticed in all the groups for the distance of infraorbital foramen from infraorbital margin. Distance of infraorbital foramen from nasal notch did not show sexual dimorphism in most of the groups except group I where value was more in males. Rule of generalized phenomenon of larger skeleton in male was not applicable in most of the groups.

La anatomía fetal, con su desarrollo en los últimos años, parece ser especialidad muy prometedora. El maxilar es la clave del esqueleto facial. Su anatomía en general y las variaciones bilaterales junto al dimorfismo sexual en particular, son de gran importancia quirúrgica y forense. Fueron estudiados 32 maxilares de 16 fetos humanos (21 semanas a 34 semanas) en los cuales se midió la longitud del surco y canal infraorbitario, anchos de los extremos de surco infraorbitario, diámetros del foramen infraorbitario y las distancias de este último desde el margen infraorbitario hasta la escotadura nasal. Las variaciones bilaterales en la mayoría de los parámetros fue en los grupos de fetos I (21-25 semanas) y II (26-30 semanas). La distancia entre el foramen infraorbitario y escotadura nasal mostró variaciones máximas en dos partes en los grupos de fetos. El canal Infraorbitario resultó ser más largo en los grupos II y III de fetos femeninos. El ancho del extremo posterior del surco infraorbitario fue menor en el grupo de fetos masculino I, igual en el grupo II y mayor en el grupo III. El dimorfismo sexual se observó en todos los grupos en la distancia desde el foramen infraorbitario hasta el margen infraorbitario. La distancia desde el foramen infraorbitario hasta la escotadura nasal no mostró dimorfismo sexual en la mayoría de los grupos a excepción del grupo I, donde el valor fue mayor en los hombres. La norma generalizada que el esqueleto más grande es del género masculino no fue aplicable en la mayoría de los grupos.

Morphometric analysis of infraorbital foramen and infraorbital canal in human feotuses / Análisis morfométrico del foramen infraorbitario y canal infraorbitario en fetos humanos

Literature regarding analysis of infraorbital foramen and canal exists in adult but it is scanty in foetuses. Morphometric measurements were performed in sixty maxillae dissected out from thirty human foetuses. The latter were divided into five groups on the basis of age i.e. groups I(<17 weeks IUL),II (17-20 weeks IUL), III (21-25 weeks IUL),IV (26-30 weeks IUL) and V (>30 weeks IUL).Four parameters considered were length of infraorbital foramen and canal and width of anterior and posterior ends of infraorbital foramen. Range of measurements between the smallest fetal group to largest fetal group for length of infraorbital foramen and canal and width at the anterior and posterior ends of infraorbital foramen were 4.01mm to 6.00 mm,0.67 mm to 2.60 mm,0.64 mm to 1.65 mm and 1.39 mm to 3.01 mm, respectively.The shape of the infraorbital foramen is maintained in most of the groups. Correlation coefficient analysis between measurements of lengths and aging foetuses is indicative of variable osteoblastic and osteoclastic activities. Enhanced osteoblastic activity seems to be an important phenomenon in postnatal life.

Existe literatura en relación con el análisis de foramen y canal infraorbitarios en adultos pero es escasa en fetos. Se realizaron mediciones morfométricas en 60 maxilares disecados de 30 fetos humanos. Los fetos fueron divididos en cinco grupos en función de la edad, es decir los grupos I (<17 semana VIU), II (17-20 semanas VIU), III (21-25 semanas VIU), IV (26-30 semanas VIU) y V (> 30 semanas VIU). Fueron considerados cuatro parámetros : longitudes del foramen y canal infraorbitario y anchos anterior y posterior de los extremos del foramen infraorbitario. El rango de las mediciones entre el grupo de fetos más pequeño al grupo más grande tanto de las longitudes del foramen y canal infraorbitario como los anchos de los extremos en la parte anterior y posterior del foramen infraorbitario fueron: 4.01mm a 6.00 mm, 0.67 mm a 2.60 mm, 0.64 mm a 1.65 mm y 1.39 mm a 3.01 mm, respectivamente. La forma del foramen infraorbitario se mantuvo en la mayoría de los grupos. El análisis del coeficiente de correlación entre las mediciones de longitudes y edades de los fetos, es indicativo de las variables de actividades osteoblástica y osteoclástica. El aumento de la actividad osteoblástica parece ser un fenómeno importante en la vida postnatal.

Effects of induced premaxillary suture fusion on the craniofacial morphology in growing rats.

OBJECTIVE: Due to premaxillary rapid development and fusion with the maxilla at the fetus stage, the functions of the premaxillary suture still remain unclear. This study was designed to explore the effect of artificial induced premaxillary suture fusion on craniofacial morphology. METHODS: Thirty Sprague Dawley rats were divided into control and experimental groups, with 3 week, 5 week and 8 week subgroups of five animals each. An incision was made in each rat along the premaxillary suture and cyanoacrylate was administered to immobilize the exposed premaxillary suture for experimental rats. No glue was applied to controls. Weights, dental impressions and radiographs were taken before and after surgery until sacrifice and used to determine the differences between groups using the one-way ANOVA test. RESULTS: After immobilizing the premaxillary suture, significant changes in the craniofacial morphology were measured at the different time points. In the experimental groups, local changes occurred at the 3rd week. A global alteration in craniofacial morphology was apparent at the 8th week in the experimental group compared to the control. At each successive time point, craniofacial morphological alterations increased in rats with fused premaxillary sutures. CONCLUSIONS: Induced premaxillary suture fusion can inhibit the growth of the premaxilla and cause extensive craniofacial morphological changes. These findings suggest that premaxillary suture fusion may be related to craniofacial malformation or malocclusion and to the formation of the flattened craniofacial profile in humans.

Development of heterodont dentition in house shrew (Suncus murinus).

Mammalian heterodont dentition comprises incisors, canines, premolars, and molars. Although there has been intensive research, the patterning of these specific tooth types has not yet been elucidated. In order for the gene expression data to be linked with tooth type determination, it is first necessary to determine precisely the incisor-, canine-, premolar-, and molar-forming regions in the jaw primordia. To accomplish this, we studied dentition development in the house shrew (Suncus murinus), which has retained all the tooth types, using three-dimensional reconstructions from serial histological sections and the Sonic hedgehog (Shh) expression patterns. Before the appearance of morphological signs of odontogenesis, Shh expression localized to the presumptive tooth-forming regions, in which the mesial and distal expression domains corresponded to the incisor- and premolar-forming regions, respectively. The upper incisor region was found to extend across the boundary between the frontonasal and the maxillary processes. The canine-forming regions later appeared in the intermediate portions of the maxillary and the mandibular processes. The molar-forming regions later appeared distal to the initially demarcated tooth-forming regions by secondary extension of the distal ends. The demarcation visualized by the Shh expression pattern in the jaw primordia of the house shrew probably represents the basic developmental pattern of mammalian heterodont dentition.

Early development of the lower deciduous dentition and oral vestibule in human embryos.

The aim of this work was to investigate the early development of the deciduous dentition and oral vestibule in the human embryonic lower jaw. Histological sections and three-dimensional reconstructions from prenatal weeks 6-9 were used. A continuous anlage for the oral vestibule did not exist in the mandible. In contrast to the upper jaw, where we previously observed that the dental and vestibular epithelia developed separately, two dento-vestibular bulges differentiated in the incisor region of the mandible. The lingual parts of each bulge were found to give rise to the respective central and lateral incisors, whereas the labial parts differentiated into the vestibular epithelium. In the canine and molar areas, the dental and vestibular epithelia originated separately. Later, the segments of the vestibular epithelium fused into the labial vestibular ridge, giving rise to the lower oral vestibule in the lip region. In the cheek region, the oral vestibule was found to originate in the mucosal inflection between the developing jaw and the cheek. A similar heterogeneous developmental base for the oral vestibule was also observed in the upper jaw. There is thus no general scheme for the early development of the dental and vestibular epithelia that applies to both the upper and lower jaws, and to both their anterior and posterior regions.