Morphometric analysis of cervical vertebrae in relation to mandibular growth.

INTRODUCTION: Cervical vertebral maturation (CVM) methods have been criticized because of their subjective nature. The aims of this study were (1) to analyze the morphometric changes in the outline of the second to fourth cervical vertebrae with growth and (2) to test the validity of the CVM method for determining the mandibular growth peak. METHODS: Lateral cephalograms of 25 participants from ages 10 to 16 years were acquired from the Burlington Growth Study, and the CVM stage was qualitatively determined. Mandibular and cervical vertebral semilandmarks were then digitized, and point distribution models were used to describe the morphometric templates of the vertebrae in relation to chronologic age and the timing of peak mandibular growth. Mixed model analysis was used to determine the relationship between mandibular length, sex, CVM stage, and chronologic age. RESULTS: Morphometric changes of the second to fourth cervical vertebrae during growth were consistent with the CVM descriptions. However, mandibular length changes were not significantly associated with CVM stages after adjusting for chronologic age. Morphometric templates of vertebral shapes before and during the mandibular growth peak were similar, with changes detectable only after the growth peak had passed. Morphometric vertebral shape changes varied between the sexes. CONCLUSIONS: Morphometric changes of the cervical vertebrae and the CVM method could not accurately identify the mandibular growth peak.

Cervical vertebral bone mineral density changes in adolescents during orthodontic treatment.

INTRODUCTION: The cervical vertebral maturation (CVM) stages have been used to estimate facial growth status. In this study, we examined whether cone-beam computed tomography images can be used to detect changes of CVM-related parameters and bone mineral density distribution in adolescents during orthodontic treatment. METHODS: Eighty-two cone-beam computed tomography images were obtained from 41 patients before (14.47 ± 1.42 years) and after (16.15 ± 1.38 years) orthodontic treatment. Two cervical vertebral bodies (C2 and C3) were digitally isolated from each image, and their volumes, means, and standard deviations of gray-level histograms were measured. The CVM stages and mandibular lengths were also estimated after converting the cone-beam computed tomography images. RESULTS: Significant changes for the examined variables were detected during the observation period (P ≤0.018) except for C3 vertebral body volume (P = 0.210). The changes of CVM stage had significant positive correlations with those of vertebral body volume (P ≤0.021). The change of the standard deviation of bone mineral density (variability) showed significant correlations with those of vertebral body volume and mandibular length for C2 (P ≤0.029). CONCLUSIONS: The means and variability of the gray levels account for bone mineral density and active remodeling, respectively. Our results indicate that bone mineral density distribution and the volume of the cervical vertebral body changed because of active bone remodeling during maturation.

A comparison of skeletal maturation in patients with tooth agenesis and unaffected controls assessed by the cervical vertebral maturation (CVM) index.

OBJECTIVE: The aims of this study were to (1) investigate if there is a difference in skeletal maturation between tooth agenesis and control patients and (2) whether skeletal maturation is affected by the severity of tooth agenesis. The cervical vertebral maturation (CVM) index can be used to assess skeletal maturation. DESIGN: A retrospective cross-sectional study. SETTING: Eastman Dental Hospital, London, UK. METHODS AND MATERIALS: A total of 360 cephalograms of patients aged 9-17 years (164 males and 196 females) allocated to four subgroups (mild, moderate and severe tooth agenesis patients, and controls) were assessed retrospectively. There were 90 patients in each of the four subgroups. The skeletal maturation of each subject was assessed both quantitatively and qualitatively using the CVM index. All patients in the study were either currently receiving treatment or had been discharged from the hospital. RESULTS: There was no statistically significant relationship between skeletal maturation and the presence of tooth agenesis. Furthermore, there was no statistically significant relationship between the skeletal maturity of patients and different severities of tooth agenesis. CONCLUSIONS: The data obtained from this group of patients and using this measurement tool alone does not supply sufficient reason to reject the null hypothesis. However, it suggests that it is possible that no difference exists between the groups.

Normal ossification patterns of atlas and axis: a CT study.

BACKGROUND AND PURPOSE: Development of the CVJ is a complex process rarely analyzed by CT. Cartilaginous remnants within the atlas and axis have been shown to variably persist throughout childhood and may be mistaken for fractures. The purpose of this study was to better estimate the fusion timeline of the synchondroses at the CVJ. MATERIALS AND METHODS: We retrospectively reviewed singular CT scans in 550 children without known skeletal dysplasia or maturation delay (from neonate to 17 years) and analyzed the ossification of atlas and axis. Normal closing age for synchondroses was defined as soon as a complete ossification rate of 80% or more per age category was achieved. RESULTS: No separate OC was observed in 38 of 230 incompletely ossified AAAs, whereas single, bipartite, or multiple OCs were observed in, respectively, 196, 86, and 16 of 298 AAAs in which OCs could be identified. Synchondroses at the AAA closed after 12 years (range 4.5-17 years). Posterior midline synchondrosis of the atlas closed after 4 years (range 2-13 years). The axis ossified from 6 OCs and 4 synchondroses. Subdental and neurocentral synchondroses closed simultaneously after 9 years (range 7-9.5 years). Apicodental synchondrosis and chondrum terminale were completely ossified after 10.5 years (range 5.5-13.5 years). CONCLUSIONS: Analysis of the CVJ using triplanar CT reconstructions allows secure identification of characteristic developmental features of the atlas and axis, and helps to separate normal variants from true osseous lesions.

An assessment of the relationship between cervical vertebrae maturation index and eruption of permanent maxillary canines.

AIM: The purpose of the present study was to establish the relationship between the eruption of permanent maxillary canines and cervical vertebral maturation stages (CVMs) to assess an alternative method for determining time of canine eruption in the late mixed dentition. MATERIALS AND METHODS: One hundred and twenty subjects with erupting permanent maxillary canines were observed both intraorally and radiographically with orthopantamograms. Lateral cephalograms were recorded to divide subjects according to CVM stage into prepeak (CS1 and CS2), peak (CS3 and CS4) and postpeak (CS5 and CS6) groups of puberty. STATISTICAL ANALYSIS: The differences between the prevalence rates of canine eruption in different groups of puberty were estimated using 'z test'. RESULTS: Prepeak group comprised of forty six subjects, peak group sixty eight subjects and postpeak group six subjects. The differences in prevalence rates between peak and prepeak and between peak and postpeak groups were noticed highly significant (p<0.001), while prevalence rates between peak and postpeak was found less significant ( p0 <0.01). CONCLUSION: Eruption of the permanent maxillary canine can occur at any CVM stage till end of the puberty or after puberty (CS1-CS6). Thus, an absence of maxillary canine during or after postpeak stage of puberty (CS5 or CS6) suggests delayed eruption and canine impaction.

Developmental anatomy of the atlas and axis in childhood by computed tomography.

OBJECT: The CT modality plays a central role in the diagnosis of cervical spine fractures. In childhood, radiolucent synchondroses between ossification centers can resemble fractures, and they can be the sites of fractures as well. Recognition of cervical spine fractures in children requires familiarity with normal developmental anatomy and common variants as they appear on CT scans. METHODS: A convenience sample of 932 CT scans of the cervical spine accessible on the picture archiving and communications system (known as PACS) at a single children's hospital was examined. Scans were excluded from further analysis if they did not include the atlantoaxial region or were otherwise technically unsatisfactory; if the patient carried the diagnosis of a skeletal dysplasia; or if there were developmental lesions noted at other levels of the spine. No more than 1 scan per patient was analyzed. Synchondroses were graded as radiolucent, not totally radiolucent but still visible, or no longer visible. Their locations and symmetries were noted. The presence or absence of the tubercles of the transverse ligament was noted as well. RESULTS: After exclusions, 841 studies of the atlas and 835 studies of the axis were analyzed. The 3 common ossification centers of the atlas arose in the paired neural arches and the anterior arch, but in as many as 20% of cases the anterior arch developed from paired symmetrical ossification centers. The 5 common ossification centers of the axis arose in the paired neural arches, in the basal center, in the dentate center (from which most of the dentate process develops), and in the very apex of the dentate process. The appearance of each synchondrosis was noted at sequential ages. The tubercles for the transverse ligament generally did not appear until the ossification of the synchondroses of the atlas was far advanced. Anomalies of the atlas included anterior and posterior spina bifida, absence of sectors of the posterior arch, and anomalous ossification centers and synchondroses. Anomalies of the axis were much less common. What appeared possibly to be chronic, incompletely healed fractures of the atlas were discovered on review for this analysis in 6 cases. No fractures of the axis were discovered. CONCLUSIONS: There is substantial variation in the time course and pattern of development of the atlas, and anomalies are common. Some fractures of the atlas may escape recognition without manifest sequelae. Variation in the time course of the development of the axis is notable as well, but anomalies seem much less common.

Evaluation of skeletal maturation by comparing the hand wrist radiograph and cervical vertebrae as seen in lateral cephalogram.

BACKGROUND AND OBJECTIVES: Aim of this study was to determine the validity of cervical vertebrae radiographic assessment to predict skeletal maturation. MATERIALS AND METHODS: Left-hand wrist and lateral cephalometric radiographs of 100 Bangalore children aged 8-18 years, divided into 10 groups of 10 subjects each with equal distribution of males and females, were measured. On left-hand wrist radiograph, the classification of Fishman was used to assess skeletal maturation. Cervical vertebrae maturation was evaluated with lateral cephalometric radiograph, using the stages developed by Hassel and Farman. The changes in hand wrist and cervical vertebrae were correlated. RESULTS: Significant association was observed between skeletal maturation indicator stages and cervical vertebrae maturation indicator stages. Correlation coefficient was found to be significant (P<0.0001). CONCLUSION: The results of the study indicated that the cervical vertebrae maturation and hand wrist skeletal maturation was significantly related.

Yes-associated protein 65 (YAP) expands neural progenitors and regulates Pax3 expression in the neural plate border zone.

Yes-associated protein 65 (YAP) contains multiple protein-protein interaction domains and functions as both a transcriptional co-activator and as a scaffolding protein. Mouse embryos lacking YAP did not survive past embryonic day 8.5 and showed signs of defective yolk sac vasculogenesis, chorioallantoic fusion, and anterior-posterior (A-P) axis elongation. Given that the YAP knockout mouse defects might be due in part to nutritional deficiencies, we sought to better characterize a role for YAP during early development using embryos that develop externally. YAP morpholino (MO)-mediated loss-of-function in both frog and fish resulted in incomplete epiboly at gastrulation and impaired axis formation, similar to the mouse phenotype. In frog, germ layer specific genes were expressed, but they were temporally delayed. YAP MO-mediated partial knockdown in frog allowed a shortened axis to form. YAP gain-of-function in Xenopus expanded the progenitor populations in the neural plate (sox2(+)) and neural plate border zone (pax3(+)), while inhibiting the expression of later markers of tissues derived from the neural plate border zone (neural crest, pre-placodal ectoderm, hatching gland), as well as epidermis and somitic muscle. YAP directly regulates pax3 expression via association with TEAD1 (N-TEF) at a highly conserved, previously undescribed, TEAD-binding site within the 5' regulatory region of pax3. Structure/function analyses revealed that the PDZ-binding motif of YAP contributes to the inhibition of epidermal and somitic muscle differentiation, but a complete, intact YAP protein is required for expansion of the neural plate and neural plate border zone progenitor pools. These results provide a thorough analysis of YAP mediated gene expression changes in loss- and gain-of-function experiments. Furthermore, this is the first report to use YAP structure-function analyzes to determine which portion of YAP is involved in specific gene expression changes and the first to show direct in vivo evidence of YAP's role in regulating pax3 neural crest expression.

Quantitative skeletal evaluation based on cervical vertebral maturation: a longitudinal study of adolescents with normal occlusion.

The study aims were to investigate the correlation between vertebral shape and hand-wrist maturation and to select characteristic parameters of C2-C5 (the second to fifth cervical vertebrae) for cervical vertebral maturation determination by mixed longitudinal data. 87 adolescents (32 males, 55 females) aged 8-18 years with normal occlusion were studied. Sequential lateral cephalograms and hand-wrist radiographs were taken annually for 6 consecutive years. Lateral cephalograms were divided into 11 maturation groups according to Fishman Skeletal Maturity Indicators (SMI). 62 morphological measurements of C2-C5 at 11 different developmental stages (SMI1-11) were measured and analysed. Locally weighted scatterplot smoothing, correlation coefficient analysis and variable cluster analysis were used for statistical analysis. Of the 62 cervical vertebral parameters, 44 were positively correlated with SMI, 6 were negatively correlated and 12 were not correlated. The correlation coefficients between cervical vertebral parameters and SMI were relatively high. Characteristic parameters for quantitative analysis of cervical vertebral maturation were selected. In summary, cervical vertebral maturation could be used reliably to evaluate the skeletal stage instead of the hand-wrist radiographic method. Selected characteristic parameters offered a simple and objective reference for the assessment of skeletal maturity and timing of orthognathic surgery.

Quantification of cranial base growth during pubertal growth.

OBJECTIVE: To quantify longitudinal cranial base growth from prepubertal through postpubertal stages of development, as defined by biological indicators of individual skeletal maturity (cervical vertebral maturation - CVM) method and to determine if there is sexual dimorphism resulting from cranial base growth. DESIGN: A longitudinal cephalometric study. SETTING: The Dental School of Paulista University, Brazil. PARTICIPANTS: 36 subjects (21 females, 15 males) who were part of a longitudinal growth study and exhibited normal facial and normal vertical growth patterns. METHODS: Growth maturation of cervical vertebrae stages was assessed by two examiners independently. Cranial base measurements were carried out by one individual and repeated after one month. The growth increments over time were assessed with the one-way repeated-measures analysis of variance and post hoc Tukey multiple comparisions. RESULTS: There were no significant gender differences. There was a significant increase in all cephalometric measures between the different time points. Ba-Na showed the greatest amount of growth (mean change=2.8 mm). From T2-T3, the greatest amount of growth was found for Se-Na (mean change=3.4 mm) and the lowest for CC-Na (mean change=1.4 mm). Comparing overall changes (T1-T3) all the measurements showed statistically significantly increases (P<0.05). For all comparisons of between-stage changes the cranial base grew more than 2.0 mm during the pubertal growth. CONCLUSIONS: Linear variables of cranial base showed significant growth during pubertal stages (pre-peak, peak and post-peak). No significant differences.

Differential expression of RARbeta isoforms in the mouse striatum during development: a gradient of RARbeta2 expression along the rostrocaudal axis.

The retinoic acid receptor RARbeta is highly expressed in the striatum of the ventral telencephalon. We studied the expression pattern of different RARbeta isoforms in the developing mouse striatum by in situ hybridization. We found a differential ontogeny of RARbeta2 and RARbeta1/3 in embryonic day (E) 13.5 lateral ganglionic eminence (striatal primordium). RARbeta2 mRNA was detected primarily in the rostral and ventromedial domains, whereas RARbeta1/3 mRNAs were enriched in the caudal and dorsolateral domains. Notably, by E16.5, a prominent decreasing gradient of RARbeta2 mRNA was present in the developing striatum along the rostrocaudal axis, i.e., RARbeta2 was expressed at higher levels in the rostral than the caudal striatum. No such gradient was found for RARbeta1/3 and RARbeta3 mRNAs. The rostrocaudal RARbeta2 gradient gradually disappeared postnatally and was absent in the adult striatum. The differential expression pattern of RARbeta isoforms in the developing striatum may provide an anatomical basis for differential gene regulation by RARbeta signaling.

Ancestral role of caudal genes in axis elongation and segmentation.

caudal (cad/Cdx) genes are essential for the formation of posterior structures in Drosophila, Caenorhabditis elegans, and vertebrates. In contrast to Drosophila, the majority of arthropods generate their segments sequentially from a posteriorly located growth zone, a process known as short-germ development. caudal homologues are expressed in the growth zone of diverse short-germ arthropods, but until now their functional role in these animals had not been studied. Here, we use RNA interference to examine the function of caudal genes in two short-germ arthropods, the crustacean Artemia franciscana and the beetle Tribolium castaneum. We show that, in both species, caudal is required for the formation of most body segments. In animals with reduced levels of caudal expression, axis elongation stops, resulting in severe truncations that remove most trunk segments. We also show that caudal function is required for the early phases of segmentation and Hox gene expression. The observed phenotypes suggest that in arthropods caudal had an ancestral role in axis elongation and segmentation, and was required for the formation of most body segments. Similarities to the function of vertebrate Cdx genes in the presomitic mesoderm, from which somites are generated, indicate that this role may also predate the origin of the Bilateria.

An improved version of the cervical vertebral maturation (CVM) method for the assessment of mandibular growth.

The present study aimed to provide a version of the Cervical Vertebral Maturation (CVM) method for the detection of the peak in mandibular growth based on the analysis of the second through fourth cervical vertebrae in a single cephalogram. The morphology of the bodies of the second (odontoid process, C2), third (C3), and fourth (C4) cervical vertebrae were analyzed in six consecutive cephalometric observations (T1 through T6) of 30 orthodontically untreated subjects. Observations for each subject consisted of two consecutive cephalograms comprising the interval of maximum mandibular growth (as assessed by means of the maximum increment in total mandibular length, Co-Gn), together with two earlier consecutive cephalograms and two later consecutive cephalograms. The analysis consisted of both visual and cephalometric appraisals of morphological characteristics of the three cervical vertebrae. The construction of the new version of the CVM method was based on the results of both ANOVA for repeated measures with post-hoc Scheffé's test (P < .05) and discriminant analysis. The new CVM method presents with five maturational stages (Cervical Vertebral Maturation Stage [CVMS] I through CVMS V, instead of Cvs 1 through Cvs 6 in the former CVM method). The peak in mandibular growth occurs between CVMS II and CVMS III, and it has not been reached without the attainment of both CVMS I and CVMS II. CVMS V is recorded at least two years after the peak. The advantages of the new version of the CVM method are that mandibular skeletal maturity can be appraised on a single cephalogram and through the analysis of only the second, third, and fourth cervical vertebrae, which usually are visible even when a protective radiation collar is worn.

N-acetyl-cysteine causes a late re-specification of the anteroposterior axis in the Xenopus embryo.

N-acetyl cysteine is an agent which has been shown to interrupt signal transduction processes linking a wide range of stimuli to the activation of NF-kappa B in mammalian cells. We have investigated its effect on the early development of Xenopus embryos by injecting it into blastulae, using concentrations comparable to those effective on cultured cells. High concentrations at the late blastula or early gastrula stage suppress posterior and enhance anterior development, yielding embryos with enlarged cement glands and otherwise consisting of little except head in extreme cases. Reducing the amount of N-acetyl cysteine injected leads to progressively more posterior structures developing. Injection into one- or two-cell embryos gives similar phenotypes, but of reduced severity and the cement gland is not so enlarged. Explants of animal cap cells taken several hours after injection develop to give large amounts of cement gland material. We have examined the expression of a number of genes in the anteriorised embryos. Posterior markers and Xsna are reduced. Noggin and Goosecoid mRNA are up-regulated through the gastrula and persist at these levels until at least the late neurula stage, whereas in controls Noggin is much lower and Goosecoid is absent at these stages. The most anteriorised phenotype may be a consequence of this changed expression.

Craniocervical junction as a focus for craniofacial growth studies.

The craniocervical junction is a highly specialized unit simultaneously supporting head during movements in all planes and protecting the spinal cord. Anatomically, it includes an atlantoaxial complex, part of which embryonically arises from the occipital region of the skull. This review deals with the gross anatomy, kinematics, and growth reactions associated with functional alteration in this complex. Particular attention is paid to the atlas, the connecting element between the head and the vertebral column proper. From several studies it is concluded that the horizontal growth of the atlas is regulated by synchondroseal growth, whereas the vertical growth is determined by appositional growth. Some vertebral anomalies and concomitant anomalies of the cranial base are reported, to point out the ontogenetic integration between the skull base and the craniocervical junction. The high frequencies of atlantal posterior arch deficiency in cleft palate patients have led to speculations about common etiologic factors in these conditions.

Comparison of mandibular growth with other variables during puberty.

The purpose of this investigation was to compare growth characteristics of the mandible during puberty with growth characteristics of the hyoid bone, cervical vertebrae, hand bones and standing height. Data were compiled from serial lateral cephalometric roentgenograms, hand-wrist roentgenograms and body height records of 33 Japanese girls between 9 and 14 years old. Records were updated annually. The mandibular growth rate differed from the other growth rates. The timing of maximum growth velocity of the mandible varied more widely than the timing of maximum growth velocity of the other parameters measured, and the total amount of mandibular growth did not correlate to any other measurement. The timing and magnitude of circumpubertal growth acceleration of various components of the body vary within a certain range of difference. However, the amount and timing of mandibular growth seems to be more variable than the other areas studied.

The odontoid process in children--is it hypoplastic?

An analysis of the cervical spine of 508 normal children aged between 3 and 18.9 years provided data for the normal development of the odontoid process and its relationship to the anterior arch of the atlas. In normal children under the age of 9 years, the tip of the odontoid may fall well short of the upper margin of the anterior arch of the atlas. This has important implications for the assessment of atlanto-axial instability in children with Down's syndrome.