Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PALATE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed2006

Effect of palate covering on bolus-propulsion time and its contributory factors.

The aim of this study was first to investigate whether the covering of the palatal mucosa with a denture base affects or not the bolus-propulsion time, and second if there was such an effect then investigate the possible contributory factors which have influence on the propulsion time. The propulsion time was measured in 21 young normal edentulous subjects under five different conditions: a complete palatal covering, non-covered palate, anterior palatal covering, posterior palatal covering and surface anaesthetized palate. As possible contributory factors palatal morphometric parameters, as well as tongue pressure were also measured. The data were analysed on the following way: changes when the palate was complete covered and non-covered, effects of sensation reduction after topic anaesthesia, effects of differences in the covering site, effects of palatal morphometric parameters and effects of tongue pressure. Ten subjects exhibited significant differences in the propulsion time when comparing the data between the complete palatal covering and the non-covered palate condition (change group). Eleven subjects did not show changes (unchanged group). Effects in the propulsion time were also recognized with posterior palatal covering-palate and superficially anaesthetized palate. With regard to the tongue pressure, significant differences during swallowing were observed. These results indicated that the bolus propulsion time into the oropharynx was affected by the palatal covering in some subjects. Moreover, the sensation in the posterior region of the hard palate, as well as the tongue pressure were also factors which affected the propulsion time during swallowing.

Adult↗
PubMed2006

Palatal size and shape in 6-year olds affected by hypohidrotic ectodermal dysplasia.

OBJECTIVE: To analyze the size and shape of the hard tissue palate of Italian subjects with hypohidrotic ectodermal dysplasia (HED). MATERIALS AND METHODS: The morphology and the dimensions of the hard tissue palate were analyzed in eight 6-year-old boys affected by HED. Four of the boys were completely edentulous and four partially dentate. Palatal landmarks were identified on stone casts and digitized with three-dimensional computerized electromagnetic instrumentation. Palatal length, slope, width, and maximum palatal height in both the sagittal and frontal planes were measured. From the coordinates of palatal landmarks, a mathematical equation of palatal shape was constructed, independent of size. HED palatal data were compared with reference data obtained from 12 healthy boys with a complete deciduous dentition. RESULTS: Palatal length and height in both the sagittal and frontal planes were significantly reduced in HED as compared with control individuals. A less steep (not significant) palatal slope was found in HED than in reference subjects, whereas similar palatal width values were observed. All palatal measurements were larger in partially dentate than in edentulous patients. Both HED and edentulousness influenced palatal shape. The HED boys had a relatively lower palate than the reference boys. In the edentulous HED boys, the hard tissue palate was relatively lower than in partially dentate HED subjects. CONCLUSIONS: Palatal size and shape were significantly modified by the presence of hypohidrotic ectodermal dysplasia, and the major alterations were found in edentulous HED subjects.

Anodontia↗
PubMed2000

Investigations on the palatal rugae pattern in cleft patients. Part I: A morphological analysis.

The characteristics of the palatal rugae zone (number of rugae, relief type, posterior limitation) were investigated on the maxillary casts of 44 patients with unilateral cleft lip and palate and 28 patients with bilateral clefts by means of reflex microscopy, a three-dimensional, computer-assisted, touch-free measuring system for the metrical registration and analysis of the parameters directly on the maxillary casts for the segments of the 2 cleft groups. The features "number of palatal rugae" and "relief type" (primary rugae) were determined both before and after surgical repair of the cleft palate. Both segments in unilateral cleft lip and palate and both lateral segments in bilateral clefts most commonly had 4 to 5 palatal rugae. The number of rugae in cleft patients is thus in a range that other authors have reported for non-cleft individuals. Following palatal cleft repair, the rugae counts per segment decreased significantly in patients with unilateral and bilateral cleft lip and palate but the 3rd rugae was never lost after surgery. The relief type identified in unilateral and bilateral cleft lip and palate was the same as in isolated cleft palates and did not differ from that in non-cleft subjects. The posterior limitation of the palatal rugae zone was determined both in a tooth-defined manner and as an absolute linear distance (at all time points). The most frequent tooth-defined posterior limitation of the rugae zone in unilateral and bilateral clefts was the second deciduous molar, which is also the position identified for non-cleft individuals. The linear distance from the tuberosity line to the rugae zone increased in all segments of unilateral and bilateral clefts during the interval up to palatal cleft repair, indicating sagittal maxillary development in the posterior area of the palate. Surgical repair of the cleft palate resulted in a significant shortening of the distance in both segments of the unilateral cleft, most likely due to the displacement of mucosa and periosteum required to cover the palatal cleft.

Chi-Square Distribution↗
PubMed2003

Palatal surface area measurement: comparisons among different cleft types.

The purpose of this study was to use three-dimensional imaging methods to measure the palatal surface of unrepaired cleft patients. The surface area of the palate was defined and measured on three-dimensional computed tomography images of dental plaster models in four different groups of cleft patients at 3 months of age. There were 30 unilateral complete cleft lips and palates (UCLP), 27 bilateral complete cleft lips and palates (BCLP), 23 isolated cleft palates of incomplete form (CP), and 19 unilateral cleft lips without cleft palates (UCL). These patients were nonsyndromic, unoperated, and without other major deformities. The dental casts were scanned, and the computed tomography data were transferred to an imaging laboratory for processing and reconstruction of three-dimensional images. Surface area of the palate was delineated, which was defined as within the alveolar crest and the line connecting both tuberosities. In UCLP and BCLP, the edge of cleft formed the medial boundary of the area for each palatal shelf, and the palatal surface area was the combination of both palatal shelves and the premaxillary area in BCLP group. The surface area was measured. Repeated definition and measurement tasks were performed for calculation of errors. The imaging data management and measurement were performed using the Analyze program (Biomedical Imaging Resource, Mayo Foundation, MN). In addition, linear distances were measured between the canine points on the alveolar crest (line C) and the tuberosity points (line T). The measurements were compared among the different groups. Analysis of variance and multiple comparisons were used for statistical analyses. The results showed that the mean error between repeated area definitions and measurements in this study was 1.86%. The bilateral complete cleft lip and palate (BCLP) and unilateral complete cleft lip and palate (UCLP) groups had significantly smaller palatal surface area than the unilateral cleft lip without cleft palate (UCL) and isolated cleft palate of incomplete form (CP) groups. There was no significant difference between the BCLP and UCLP groups. Line C and line T distances were significantly longer in BCLP and UCLP groups than in UCL and CP groups. The findings suggest that compared with UCL and CP patients, there is an intrinsic tissue deficiency in the palate/maxilla of BCLP and UCLP patients.

Cleft Lip↗
PubMed2002

Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis.

Cleft palate, the most frequent congenital craniofacial birth defects in humans, arises from genetic or environmental perturbations in the multi-step process of palate development. Mutations in the MSX1 homeobox gene are associated with non-syndromic cleft palate and tooth agenesis in humans. We have used Msx1-deficient mice as a model system that exhibits severe craniofacial abnormalities, including cleft secondary palate and lack of teeth, to study the genetic regulation of mammalian palatogenesis. We found that Msx1 expression was restricted to the anterior of the first upper molar site in the palatal mesenchyme and that Msx1 was required for the expression of Bmp4 and Bmp2 in the mesenchyme and Shh in the medial edge epithelium (MEE) in the same region of developing palate. In vivo and in vitro analyses indicated that the cleft palate seen in Msx1 mutants resulted from a defect in cell proliferation in the anterior palatal mesenchyme rather than a failure in palatal fusion. Transgenic expression of human Bmp4 driven by the mouse Msx1 promoter in the Msx1(-/-) palatal mesenchyme rescued the cleft palate phenotype and neonatal lethality. Associated with the rescue of the cleft palate was a restoration of Shh and Bmp2 expression, as well as a return of cell proliferation to the normal levels. Ectopic Bmp4 appears to bypass the requirement for Msx1 and functions upstream of Shh and Bmp2 to support palatal development. Further in vitro assays indicated that Shh (normally expressed in the MEE) activates Bmp2 expression in the palatal mesenchyme which in turn acts as a mitogen to stimulate cell division. Msx1 thus controls a genetic hierarchy involving BMP and Shh signals that regulates the growth of the anterior region of palate during mammalian palatogenesis. Our findings provide insights into the cellular and molecular etiology of the non-syndromic clefting associated with Msx1 mutations.

Animals↗
PubMed1976

Prosthodontic aspects of palatal elevation and palatopharyngeal stimulation.

The prosthodontic aspects of palatal elevation and palatopharyngeal stimulation were discussed. Following are important factors that must be considered. (1) Elevation of the soft palate should be gradual to avoid placing pressure upon the teeth retaining the prosthesis and to reduce mucosal irritation. (2) Prosthetic stimulation should be initiated as soon as palatal paralysis is noted to prevent palatal disuse atrophy. (3) The palatal lift prosthesis may be used as a temporary or definitive treatment for palatal incompetency. When adequate elevation of the soft palate has been achieved, the prosthesis may be discarded. Otherwise, the patient would wear the prosthesis as a permanent supportive device. (4) The construction of the combined palatal lift/pharyngeal section prosthesis includes the gradual palatal elevation and molding of the pharyngeal section to reduce the gag reflexes and to increase palatopharyngeal muscle adaptation to the prosthesis. After the initial placement, adjustment to the pharyngeal section is easier for the patient. (5) Speech and myofunctional therapy should be instituted in conjunction with prosthetic treatment. (6) The palatal lift and combination prostheses are more effective for patients with less severe neurologic impairment and speech articulatory problems. (7) The palatal lift prosthesis is more effective for those patients with palatal incompetency who have no involvement of the other oropharyngeal muscles. The combination type of prosthesis is more effective for patients with palatopharyngeal insufficiency without marked speech articulatory disorders. There are still several questions which require further investigation. These include: (1) What is the relationship between the palatal stimulation and the degree of neuromuscular function and recovery? (2) What is the relationship between the palatal stimulation and the degree of palatal disuse atrophy? (3) What is the relationship between pharyngeal stimulation and muscle contraction? (4) What is the degree of stability of palatopharyngeal function and muscle contraction after stimulation?

Denture Design↗
PubMed1998

Morphology of isolated cleft palate in children, including Robin sequence, treated with one or two-stage operations.

A classification developed at the Uppsala Cleft Palate Centre was used to describe isolated cleft palate in children with and without Robin sequence. The study included 109 patients born between 1968 and 1983 with isolated cleft palate. In 46 patients the cleft was closed in a single operation and 63 were treated by a two-stage procedure. Of the 109 patients 70 (64%) were girls. In 19 patients (17%), the cleft was limited to the soft palate. Ninety of the patients had clefts of the hard palate and in 39 (43%) of these patients the clefts involved less than a third of the hard palate. Only four children (4%) had total clefts of both the hard and soft palate. The Robin sequence was diagnosed in 14 children (13%), and it was more common in boys with isolated cleft palate (7/39; 18%) than in girls (7/70; 10%). In those with Robin sequence the cleft was U-shaped anteriorly in nine (64%), with great variations in width. Generally, however, the clefts were wider than other clefts involving the hard palate. In all cases, closure of the soft palate was followed by a spontaneous reduction in the width of the remaining cleft in the hard palate. The greatest improvement was noted in subjects with the U-shaped clefts, in whom the position of the tongue probably had the greatest influence on the development of wide primary clefts. In 10 subjects with clefts of the soft palate only and 12 patients in whom the cleft included part of the hard palate (35%), only the first operation of the two-stage procedure was done because there was no residual cleft. In these subjects the original cleft had involved less than a third of the length of the hard palate.

Child, Preschool↗
PubMed2002

Rescue of an in vitro palate nonfusion model using interposed embryonic mesenchyme.

The authors previously established an in vitro palate nonfusion model on the basis of a spatial separation between prefusion embryonic day 13.5 mouse palates (term gestation, 19.5 days). They found that an interpalatal separation distance of 0.48 mm or greater would consistently result in nonfusion after 4 days in organ culture. In the present study, they interposed embryonic palatal mesenchymal tissue between embryonic day 13.5 mouse palatal shelves with interpalatal separation distances greater than 0.48 mm in an attempt to "rescue" this in vitro palate nonfusion phenotype. Because no medial epithelial bilayer (i.e., medial epithelial seam) could potentially form, palatal fusion in vitro was defined as intershelf mesenchymal continuity with resolution of the medial edge epithelia bilaterally. Forty-two (n = 42) palatal shelf pairs from embryonic day 13.5 CD-1 mouse embryos were isolated and placed on cell culture inserts at precisely graded distances (0, 0.67, and 0.95 mm). Positive controls consisted of shelves placed in contact (n = 6). Negative controls consisted of shelves placed at interpalatal separation distances of 0.67 mm (n = 6) and 0.95 mm (n = 7) with no interposed mesenchyme. Experimental groups consisted of embryonic day 13.5 palatal shelves separated by 0.67 mm (n = 11) and 0.95 mm (n = 12) with interposed lateral palatal mesenchyme isolated at the time of palatal shelf harvest. Specimens were cultured for 4 days (n = 19) or 10 days (n = 23), harvested, and evaluated histologically. All positive controls at 4 and 10 days in culture showed complete histologic palatal fusion. All negative controls at 4 days and 10 days in culture remained unfused. Five of six palatal shelves separated at 0.67 mm interpalatal separation distance with interposed mesenchyme were fused at 4 days, and all five were fused at 10 days. At an interpalatal separation distance of 0.95 mm with interposed mesenchyme (n = 12), no palates (zero of four) were fused at 4 days, but seven of eight were fused at 10 days. These data suggest that nonfused palatal shelves can be "rescued" with an interposed graft of endogenous embryonic mesenchyme to induce fusion in vitro.

Animals↗
PubMed2000

[Applied anatomy of arterial supply for the soft palate].

OBJECTIVE: The correct design of a myomucosal or mucosal flap of the soft palate in the surgical procedure for cleft palate and velopharyngeal incompetence should be made with a thorough knowledge of the arterial supply for the soft palate, which is an important premise for functional rehabilitation of the soft palate postoperatively. METHODS: Anatomical dissection was undertaken in 14 cadavers (10 normal adults, 2 normal newborns and 2 newborns with cleft lip & palate). The arteriography and histological studies have been used in 10 newborn and 6 aborted fetuses. RESULTS: The results showed that the arterial supply of the soft palate is multi-original and the principal artery is the ascending palatal artery. Its anterior and posterior branches are myomucosal perforators. The other vessels to supply the soft palate are direct mucosal branches, which include the lesser palatine artery, the palatal branch of the ascending pharyngeal artery and the tonsillar artery. All above arteries anastomose under the mucosal, muscular and fascial layers in the soft palate. In cleft cases, all arteries in the soft palate are displaced anterior-laterally because of the deformities of the palatal muscles and bone structure. CONCLUSIONS: This study supports the facts that the major blood supply of the soft palate comes from ascending palatine artery and the generous arterial anastomosis of the velum allows it to tolerate the proper dissection during palatoplasty. We believe that decreasing the damage of the intrapalatal vascular supply by carefully dissection around the hamulus is very important to prevent wound break down, muscular fibrosis, flap failure, and also is the basis of design for surgical procedure and postoperative functional recovery in cleft palate patients.

Adult↗
PubMed1980

Cell behaviour and cleft palate in the mutant mouse, amputated.

Cleft palate with a genetic origin normally arises because of a failure of the palatal shelves to elevate or fuse. Until now attention in studies of palatal development development has been focused on two critical phases, those of elevation and fusion. In the mutant mouse, amputated, however, cleft palate arise because of a failure of the palatal shelves to make any significant outgrowth between the 12th day after conception when the palatal shelves are first observed and the 14th day when elevation and fusion normally occur. When cell proliferation (mitotic index) was measured in the palatal shelves on days 12, 13 and 14 no difference was found between mutant and normal. The failure of the mutant palate to grow cannot be accounted for on grounds of reduced cell proliferation. For this reason the palatal mesenchyme in 12.5-day and 14.5-day normal and amputated mice has been studied wit the scanning electron microscope. This work shows that the mesenchymal cells in the mutant palate are clumped together and have much greater areas of cell contact than are observed in the normal palate. The abnormal cell behaviour described in mutant palatal mesenchyme is typical of amputated embryonic mesenchyme in general, and in other cases has been shown to cause abnormal morphogenesis. We propose that aberrant cell behaviour causing an aggregation through increased cell adhesion inhibits palatal outgrowth in the mutant, and for this reason the palatal shelves subsequently fail to elevate and fuse.

Animals↗
PubMed1999

Long-term effect of neonatal endotracheal intubation on palatal form and symmetry in 8-11-year-old children.

Premature and low birth weight infants often require neonatal oral intubation for resuscitation and to relieve respiratory distress. The endotracheal tube exerts pressure on the developing palate, which can result in palatal groove formation, a high-arched palate, and palatal asymmetry. The purpose of this investigation was to determine whether such intubation can have a long-term effect on palatal form and symmetry. Arch widths, palatal widths, and palatal depths were measured from the study casts of 43, 8-11-year-old previously intubated premature and low birth weight children using a reflex microscope, with a fixed rectangular Cartesian co-ordinate system, and compared with a group of non-intubated gender- and age-matched controls. Significant differences were found between the intubated and non-intubated children. The intubated children had significantly narrower palatal widths posteriorly (P < or = 0.001), steeper palatal vaults anteriorly (P < or = 0.01), and exhibited a directional palatal width asymmetry with the left side of the palate measuring consistently wider than the right. These differences did not, however, appear to be affected by the length of intubation. Therefore, it is concluded that an oral endotracheal tube might exert excess force on the developing alveolus anteriorly with the tube being displaced to the right of the palate posteriorly leading to a steep anterior palatal vault and a left-sided palatal asymmetry, which can persist until the age of 11 years of age.

Analysis of Variance↗
PubMed2006

Antenatal transabdominal ultrasound detection of cleft lip and palate in Western Australia from 1996 to 2003.

OBJECTIVE: To determine the frequency of detection of cleft lip with or without cleft palate and isolated cleft palate from antenatal ultrasound examinations conducted on mothers of infants born with cleft lip and/or palate and isolated cleft palate in Western Australia from 1996 to 2003. DESIGN: Review of patient records and purpose-designed questionnaire sent to parents of children born with cleft lip and/or palate and isolated cleft palate. RESULTS: There were 308 infants born with cleft lip and/or palate and isolated cleft palate in the study period. Of the 293 parents, 218 responses were available for the study (70.7%), and 2.9 +/- 1.8 SD antenatal ultrasound scans were performed on 216 women. No such scans were performed on two women. Cleft lip and/or palate was detected in 22.2% of cases. There was no detection prior to 15 weeks gestational age in the 137 women screened. Between 15 and 19 weeks gestational age, 174 scans detected 30 cases. Between 20 and 29 weeks gestational age, 84 scans detected 11 cases. Between 30 and 40 weeks gestational age, 66 scans detected 7 cases. The detection rate for bilateral cleft lip and/or palate was 44.4% and for unilateral cleft lip and/or palate, 40.6%. Detection rate for isolated cleft lip was 33.3%. Antenatal ultrasound failed to detect any infants with an isolated cleft palate (n = 95). The rate of detection of cleft lip and/or palate increased through the study period. CONCLUSIONS: The rate of detection of cleft lip and/or palate in Western Australia is comparable to that for referral centers worldwide and is increasing. The rate of detection of the various types of cleft anomalies using antenatal ultrasound ranged from 0% to 44%.

Cleft Lip↗
PubMed1999

Effects of TGFbeta2 on collagen synthesis in cultured normal and wounded fetal mouse palates.

OBJECTIVE: It has been demonstrated in a number of models that fetal wounds heal with little or no scar. Since collagen is an integral part of the extracellular matrix in adult scar formation, we studied the synthesis and localization of collagen in an in vitro mouse palate model for fetal wound healing. METHODS: Palates, dissected from fetal mice at 15, 16, and 17 days of gestation and from newborn mice, were cultured in medium containing serum (for 8 hours); this was followed by culture in serum-free medium (for 12 hours). One-half of the samples from each age group were wounded in the midline. All samples were placed in serum-free medium containing 20 microCi/mL 3H-proline for 8 hours. In addition, palates from 15-day gestation and from newborn mice were also incubated with transforming growth factor TGF-beta2 (10 ng/mL). Palates were washed with saline, homogenized, and radioactivity was counted. Proline uptake was calculated for each sample as counts per milligram of protein and was subjected to statistical analysis (three-way analysis of variance). Samples of the homogenate were subjected to sodium dodecyl sulfate-gel electrophoresis and Western blotting in order to determine the types of collagen that were synthesized. Immunohistochemical localization of collagen types I, III, and VI was carried out on paraffin-embedded samples from each group. RESULTS: There were no significant differences in proline uptake between wounded mouse palates and nonwounded mouse palates at any age, and there was no histological evidence of regeneration of the palate at the site of the wound. Proline uptake was significantly greater in untreated wounded palates at 15 days' gestation than it was in newborns. After treatment with TGF-beta2, proline uptake was significantly greater in both wounded and nonwounded palates in the newborn group and had no effect on collagen synthesis in palates from 15-day gestation animals. Collagen types I and III were localized in histological specimens using immunohistochemistry and on nitrocellulose using Western blotting. No type VI collagen was demonstrated by Western blotting, but it was localized around blood vessels and on basement membranes using immunohistochemistry. CONCLUSION: Treatment with TGF-beta2 significantly increased collagen synthesis, as assessed by 3H-proline uptake, in cultured palates from newborn mice as compared with palates from untreated newborn mice and from both treated and untreated palates of 15-day gestation mice. These data suggest a differential response to TGF-beta2 by mouse palates as a function of fetal development.

Analysis of Variance↗
PubMed2000

The effect of ethnicity and age on palatal size and shape: a study in a northern Chilean healthy population.

Race and ethnicity influence the form of the human craniofacial complex in varying ways. The aim of the present investigation was to quantify the effects of ethnicity (mestizos, Aymara, non-Aymara), age (adolescents and adults), and sex on the form (size and shape) of the hard palate in normal Native American individuals. From the dental casts of 51 individuals with a complete permanent dentition, the x, y, and z coordinates of several standardized palatal landmarks were obtained with a computerized 3-dimensional digitizer. Palatal landmarks were used to derive a mathematical equation for palatal shape in the frontal and sagittal planes. Palatal width and length, frontal and sagittal heights, sagittal slope, and deviation of the raphe from the midline were also calculated. In the Aymara subjects, there was no effect of sex on palatal size, but there was an effect on palatal shape independent of size, especially with respect to male growth. Indeed, female palates apparently did not change their shape between adolescence and adulthood, while male palates increased their posterior "height." Overall, the 3 ethnic groups appeared to possess similar palatal size, with small significant differences. In the adult individuals, ethnicity did not seem to influence palatal shape. In contrast, adolescent males showed differences: non-Aymara subjects had the "highest" palatal shape, Aymara the "lowest," and mestizos an intermediate position. In conclusion, ethnicity does not seem to be a factor of major variability of human hard palate morphology, at least in the present 3 northern Chilean groups, as already found for dental arch shape. Age probably has a larger effect, particularly in the posterior part of the palate, where the eruption of the second and third molars between adolescence and young adulthood may play a role. A further development of the present investigation may involve larger samples of individuals from different ethnic groups.

Adolescent↗
PubMed1992

Differential expression of insulin-like growth factors I and II (IGF I and II), mRNA, peptide and binding protein 1 during mouse palate development: comparison with TGF beta peptide distribution.

Development of the mammalian secondary palate involves a series of epithelial mesenchymal interactions: during one of these, a mesenchymal signal specifies regionally distinct palatal epithelial differentiation. Extracellular matrix molecules and soluble growth factors may be involved in this signalling process. In this study, we have mapped the expression of the genes for insulin-like growth factors (IGF I and II), the peptides they encode, and the IGF binding protein 1 (IGF BP-1) during murine palatogenesis (embryonic days (E) 12-15). IGF-I gene expression was below detectable levels in the craniofacial region at all ages. IGF-I peptide was at the threshold of immunocytochemical detection and widely distributed in the palatal mesenchyme, decreasing in staining intensity from E12 to E14. By contrast, IGF-II mRNA was intensely localised in several tissues. IGF-II gene expression within the forming palate was developmentally regulated. In the vertical palatal shelves (E12 to E13) IGF-II gene expression was absent. On early E14, in the horizontal prefusion palate, significant expression was present in the palatal mesenchyme, but not the epithelium. Once palatal fusion had occurred, mesenchymal expression fell rapidly to undetectable levels. IGF-II mRNA was next detectable in the secondary palate on late E15 at sites of membranous bone formation. By contrast to the mRNA distribution, IGF-II peptide was localised predominantly in the palatal epithelia (particularly the nasal and medial edge epithelia) but also in the mesenchyme of the E14 prefusion palate. Significantly, the IGF binding protein had a similar distribution pattern to the IGF-II peptide. At all ages, the developing tongue myotubes labelled heavily for IGF-II mRNA, protein and binding protein. These data suggest that IGF-II may play a localised paracrine role during murine palatogenesis, perhaps in the mesenchymal signalling of epithelial differentiation. IGF-II may also serve to coordinate the development of the tongue and palate. The distribution of IGF-II peptide was very similar to that of TGF-beta, suggesting a possible interactive role of these growth factors during palate development. Finally, evidence that the IGF-II gene is imprinted (Ferguson-Smith et al. 1991) and may be the target for uniparental disomy in the human Beckwith Wiedemann syndrome (Henry et al. 1991), which is characterised by the overgrowth of tissues (especially the tongue) expressing IGF II in the embryo, indicates the necessity of reanalysing human cleft palate families for disruption (including uniparental disomy) of the genes encoding IGFs, their receptors and binding proteins.

Animals↗
PubMed2004

Transforming growth factor beta (TGFbeta) signalling in palatal growth, apoptosis and epithelial mesenchymal transformation (EMT).

Formation of the medial edge epithelial (MEE) seam by fusing the palatal shelves is a crucial step of palate development. The opposing shelves adhere to each other at first by adherens junctions, then by desmosomes in the MEE. The MEE seam disappears by epithelial mesenchymal transformation (EMT), which creates confluence of connective tissue across the palate. Cleft palate has a mutifactorial etiology that often includes failure of adherence of apposing individual palatal shelves and/or EMT of the MEE. In this review, we first discuss TGFbeta biology, including functions of TGFbeta isoforms, receptors, down stream transcription factors, endosomes, and signalling pathways. Different isoforms of the TGFbeta family play important roles in regulating various aspects of palate development. TGFbeta1 and TGFbeta2 are involved in growth, but it is TGFbeta3 that regulates MEE transformation to mesenchyme to bring about palatal confluence. Its absence results in cleft palate. Understanding of TGFbeta family signalling is thus essential for development of therapeutic strategies. Because TGFbeta3 and its downstream target, LEF1, play the major role in epithelial transformation, it is important to identify the signalling pathways they use for palatal EMT. Here, we will discuss in detail the mechanisms of palatal seam disappearance in response to TGFbeta3 signalling, including the roles, if any, of growth and apoptosis, as well as EMT in successful MEE adherence and seam formation. We also review recent evidence that TGFbeta3 uses Smad2 and 4 during palatal EMT, rather than beta-Catenin, to activate LEF1. TGFbeta1 has been reported to use non-Smad signalling using RhoA or MAPKinases in vitro, but these are not involved in activation of palatal EMT in situ. A major aim of this review is to document the genetic mechanisms that TGFbeta uses to bring about palatal EMT and to compare these with EMT mechanisms used elsewhere.

Animals↗
PubMed2006

Cell autonomous requirement for Tgfbr2 in the disappearance of medial edge epithelium during palatal fusion.

Palatal fusion is a complex, multi-step developmental process; the consequence of failure in this process is cleft palate, one of the most common birth defects in humans. Previous studies have shown that regression of the medial edge epithelium (MEE) upon palatal fusion is required for this process, and TGF-beta signaling plays an important role in regulating palatal fusion. However, the fate of the MEE and the mechanisms underlying its disappearance are still unclear. By using the Cre/lox system, we are able to label the MEE genetically and to ablate Tgfbr2 specifically in the palatal epithelial cells. Our results indicate that epithelial-mesenchymal transformation does not occur in the regression of MEE cells. Ablation of Tgfbr2 in the palatal epithelial cells causes soft palate cleft, submucosal cleft and failure of the primary palate to fuse with the secondary palate. Whereas wild-type MEE cells disappear, the mutant MEE cells continue to proliferate and form cysts and epithelial bridges in the midline of the palate. Our study provides for the first time an animal model for soft palate cleft and submucous cleft. At the molecular level, Tgfb3 and Irf6 have similar expression patterns in the MEE. Mutations in IRF6 disrupt orofacial development and cause cleft palate in humans. We show here that Irf6 expression is downregulated in the MEE of the Tgfbr2 mutant. As a recent study shows that heterozygous mutations in TGFBR1 or TGFBR2 cause multiple human congenital malformations, including soft palate cleft, we propose that TGF-beta mediated Irf6 expression plays an important, cell-autonomous role in regulating the fate of MEE cells during palatogenesis in both mice and humans.

Animals↗
PubMed1994

Histochemical analysis of cleft palate muscle.

Research has clarified the abnormal insertions and orientations of the involved musculature in cleft palate. However, little is known about the physiologic aspects of these muscles, specifically from a histochemical perspective. In this study, 30 muscle specimens were removed from the palatal cleft margin in patients undergoing primary palatoplasty. Nine patients had combined cleft lip and palate deformity, and seven had an isolated cleft palate. Biopsies were taken from the area of the musculus uvulus in all specimens and examined by histochemical techniques. The percentage of type 1 and type 2 fibers was different in isolated cleft palate as compared with cleft lip and palate specimens, being, respectively, 56.7 percent type 1 and 43.3 percent type 2 and 62.0 percent type 1 and 38.0 percent type 2 fibers. This is the opposite ratio from other facial muscles but is in line with the literature regarding normal palatal muscle. Isolated cleft palate muscle fibers also were minimally decreased in diameter as compared with normal facial muscle. Fiber diameters of the combined cleft lip and palate muscles were severely decreased in size compared with those muscles found in the cleft lip. Abnormal mitochondrial accumulations also were found in cleft lip and palate muscle specimens but not in isolated cleft palate muscle specimens. We consider the decrease in muscle diameter found in isolated cleft palate to be secondary to functional atrophy, while that in the cleft lip and palate specimens is secondary to a primary hypoplasia together with a functional atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗