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.

SourceResearch connectionFrom yearThrough year

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

At least 523 records · Page 29Linked to original sources

PubMed2000

Sutural expansion osteogenesis for management of the bony-tissue defect in cleft palate repair: experimental studies in dogs.

A series of experimental studies on sutural expansion osteogenesis for management of the bony-tissue defect in cleft palate repair was performed between 1995 and 1997. Forty-five young dogs in weaning were used in four experiments that were divided into two parts. Part I probed the possibility of closing the surgically constructed hard palate cleft not only with mucoperiosteum but also with bony tissue by the technique of sutural expansion of lateral palatine sutures. Part II explored the possibility of pushing the palatine bone posteriorly and advancing the maxillary segment anteriorly by transverse palatine suture expansion. In Part I, a ring-shaped suture expander made of nickel-titanium shape memory alloy was used to expand the lateral suture of palatine bones. Expansion forces of 200 G, 360 G, and 480 G were used for the first experiment. A force of 360 G was chosen for two other experiments; this force is equivalent to the distraction rate of 0.5 mm per day of a jackscrew device. The ring-shaped suture expander was opened and its two feet were fixed in the medial sides of residual horizontal plates of the palatine bones immediately after a hard palate cleft was constructed surgically under endotracheal general anesthesia. At the eighth postoperative day, under the traction of 360 G, the two sides of the 8-mm-wide hard palate cleft were brought into contact with each other, and 8 or 9 days later the closed palatal cleft had healed completely with mucosal tissue. This experiment was repeated twice and yielded the same results. Sutural expansion osteogenesis was evaluated physically, fluorescently, histologically, and ultrastructurally to examine the deposition of the regenerated bone in the suture areas. Additionally, the influence of sutural expansion osteogenesis of the palatal bones on other facial bones was also studied cephalometrically. In Part II, a bow-shaped suture expander made of nickel-titanium shape memory alloy was applied to expand either the left or the right side of the transverse palatal suture of each of the experimental dogs. At the postoperative week 4 to 6, the maxillary segment was moved forward 5 to 6 mm on the expanded side, and the palatal bone was pushed backward 5 mm. The changes of bone position were assessed radiographically and cephalometrically. Tissue response of circum-maxillary sutures was examined histologically. These experiments led to the following conclusions: (1) Bony closure of the surgically constructed hard palate cleft with a ring-shaped suture expander made of nickel-titanium shape memory alloy is possible. (2) Anterior advancement of the maxillary segment and posterior lengthening of the hard palate using a bow-shaped suture expander made of nickel-titanium shape memory alloy applied at the palatomaxillary suture (transverse palatal suture) of the hard palate are also possible. Thus, in humans, a new approach for cleft palate repair may be a worthwhile investigation.

Alloys↗

PubMed1999

Pathogenesis of cleft palate in TGF-beta3 knockout mice.

We previously reported that mutation of the transforming growth factor-beta3 (TGF-beta3) gene caused cleft palate in homozygous null (-/-) mice. TGF-beta3 is normally expressed in the medial edge epithelial (MEE) cells of the palatal shelf. In the present study, we investigated the mechanisms by which TGF-beta3 deletions caused cleft palate in 129 x CF-1 mice. For organ culture, palatal shelves were dissected from embryonic day 13.5 (E13.5) mouse embryos. Palatal shelves were placed singly or in pairs on Millipore filters and cultured in DMEM/F12 medium. Shelves were placed in homologous (+/+ vs +/+, -/- vs -/-, +/- vs +/-) or heterologous (+/+ vs -/-, +/- vs -/-, +/+ vs +/-) paired combinations and examined by macroscopy and histology. Pairs of -/- and -/- shelves failed to fuse over 72 hours of culture whereas pairs of +/+ (wild-type) and +/+ or +/- (heterozygote) and +/-, as well as +/+ and -/- shelves, fused within the first 48 hour period. Histological examination of the fused +/+ and +/+ shelves showed complete disappearance of the midline epithelial seam whereas -/- and +/+ shelves still had some seam remnants. In order to investigate the ability of TGF-beta family members to rescue the fusion between -/- and -/- palatal shelves in vitro, either recombinant human (rh) TGF-beta1, porcine (p) TGF-beta2, rh TGF-beta3, rh activin, or p inhibin was added to the medium in different concentrations at specific times and for various periods during the culture. In untreated organ culture -/- palate pairs completely failed to fuse, treatment with TGF-beta3 induced complete palatal fusion, TGF-beta1 or TGF-beta2 near normal fusion, but activin and inhibin had no effect. We investigated ultrastructural features of the surface of the MEE cells using SEM to compare TGF-beta3-null embryos (E 12. 5-E 16.5) with +/+ and +/- embryos in vivo and in vitro. Up to E13.5 and after E15.5, structures resembling short rods were observed in both +/+ and -/- embryos. Just before fusion, at E14.5, a lot of filopodia-like structures appeared on the surface of the MEE cells in +/+ embryos, however, none were observed in -/- embryos, either in vivo or in vitro. With TEM these filopodia are coated with material resembling proteoglycan. Interestingly, addition of TGF-beta3 to the culture medium which caused fusion between the -/- palatal shelves also induced the appearance of these filopodia on their MEE surfaces. TGF-beta1 and TGF-beta2 also induced filopodia on the -/- MEE but to a lesser extent than TGF-beta3 and additionally induced lamellipodia on their cell surfaces. These results suggest that TGF-beta3 may regulate palatal fusion by inducing filopodia on the outer cell membrane of the palatal medial edge epithelia prior to shelf contact. Exogenous recombinant TGF-beta3 can rescue fusion in -/- palatal shelves by inducing such filopodia, illustrating that the effects of TGF-beta3 are transduced by cell surface receptors which raises interesting potential therapeutic strategies to prevent and treat embryonic cleft palate.

Animals↗

PubMed1998

Location and distribution of epithelial pearls and tooth buds in human fetuses with cleft lip and palate.

OBJECTIVE: The purpose of this study was to establish the location and distribution of epithelial pearls and tooth buds in cleft palate fetuses, relative to the time of palate fusion. DESIGN: The facial skeletal structures, dental laminae, tooth buds, and epithelial pearls were examined in seven spontaneously aborted human fetuses, of which five had unilateral or bilateral cleft lip and palate or cleft palate. The sectioned fetuses were reconstructed by 3D-computer technology. RESULTS: Epithelial pearls were found in four of the investigated cases, of which one was a control specimen. They were located at the margins of the palatal shelves. In the cleft lip and palate cases, the cleft was found in the premaxilla between the first and second incisor tooth. The premaxilla was found to be hypoplastic in both bilateral cleft lip and palate cases and was totally absent in the unilateral cleft lip and palate case. The maxilla was hypoplastic in one case with unilateral cleft lip and palate. In all other specimens, it was developed symmetrically. CONCLUSIONS: The results indicate that cleft lip and palate development may occur after the fusion of the frontonasal prominence with the maxillary prominence and the palatal shelves, as well as a nonfusion of the palatal shelves in the secondary palate.

Cleft Lip↗

PubMed2003

[Study on etiology of retinoic acid-induced cleft palate in mouse].

OBJECTIVE: To investigate the morphologic changes of embryonic palatal development exposed to retinoic acid (RA) in mouse, and to detect the significance of the expression of TGFbeta1, TGFbeta3, EGF and BCL2. METHODS: The stage of palatal development was examined by light microscopy. S-P immunohistochemistry and in-situ hybridization was used to detect spatio-temporal patterns of expression of TGFbeta1, TGFbeta3, EGF and BCL2 in embryonic palate. RESULTS: The fetus exposed to RA resulted in formation of small palatal shelves without contact and fusion of each other to form and intact palate. RA can regulate the embryonic palatal expression of genes involved in RA-induced cleft palate. CONCLUSIONS: RA can inhibit the proliferation of MEPM cell to form small palatal shelves and induce abnormal differentiation of MEE cell causing the bi-palatal shelves no contact and fuse with each other, then induce the formation of cleft palate. RA can regulate the spatio-temporal patterns of expression of TGFbeta1, TGFbeta3 and EGF in embryonic palatal processes and the change of special expression of these genes in embryonic palatal processes are involved in RA-induced cleft palate.

Abnormalities, Drug-Induced↗

PubMed1991

Cleft palate fistulas: a multivariate statistical analysis of prevalence, etiology, and surgical management.

A retrospective, multivariate statistical analysis of 129 consecutive nonsyndromic patients undergoing cleft palate repair was performed to document the incidence of postoperative fistulas, to determine their cause, and to review methods of surgical management. Nasal-alveolar fistulas and/or anterior palatal fistulas that were intentionally not repaired were excluded from study. Cleft palate fistulas (CPFs) occurred in 30 of 129 patients (23 percent), although nearly a half were 1 to 2 mm in size. Extent of clefting, as estimated by the Veau classification, was significantly more severe in those patients who developed cleft palate fistula. Type of palate closure also influenced the frequency of cleft palate fistula. Forty-three percent of patients undergoing Wardill-type closures developed cleft palate fistula versus 10, 22, and 0 percent for Furlow, von Langenbeck, and Dorrance style closures, respectively. The fistula rate was similar in patients with (30 percent) and without (25 percent) intravelar veloplasty. Age at palate closure did not significantly affect the rate of fistulization; however, the surgeon performing the initial closure did not have an effect. Thirty-seven percent of patients developed recurrent cleft palate fistulas following initial fistula repair. Recurrence of cleft palate fistulas was not influenced by severity of cleft or type of original palate repair. Following end-stage management, a second cleft palate fistula recurrence occurred in 25 percent of patients. Continued open discussion of results of cleft palate repair is recommended.

Adolescent↗

PubMed2006

Jag2-Notch1 signaling regulates oral epithelial differentiation and palate development.

During mammalian palatogenesis, palatal shelves initially grow vertically from the medial sides of the paired maxillary processes flanking the developing tongue and subsequently elevate and fuse with each other above the tongue to form the intact secondary palate. Pathological palate-mandible or palate-tongue fusions have been reported in humans and other mammals, but the molecular and cellular mechanisms that prevent such aberrant adhesions during normal palate development are unknown. We previously reported that mice deficient in Jag2, which encodes a cell surface ligand for the Notch family receptors, have cleft palate associated with palate-tongue fusions. In this report, we show that Jag2 is expressed throughout the oral epithelium and is required for Notch1 activation during oral epithelial differentiation. We show that Notch1 is normally highly activated in the differentiating oral periderm cells covering the developing tongue and the lateral oral surfaces of the mandibular and maxillary processes during palate development. Oral periderm activation of Notch1 is significantly attenuated during palate development in the Jag2 mutants. Further molecular and ultrastructural analyses indicate that oral epithelial organization and periderm differentiation are disrupted in the Jag2 mutants. Moreover, we show that the Jag2 mutant tongue fused to wild-type palatal shelves in recombinant explant cultures. These data indicate that Jag2-Notch1 signaling is spatiotemporally regulated in the oral epithelia during palate development to prevent premature palatal shelf adhesion to other oral tissues and to facilitate normal adhesion between the elevated palatal shelves.

Animals↗

PubMed1981

Correlation between alterations in Meckel's cartilage and induction of cleft palate with beta-aminoproprionitrile in the rat.

The lathyrogen beta-aminoproprionitrile (BAPN) induces cleft palate in rats when administered at a critical time in secondary palate formation. BAPN is known to inhibit the crosslinking of newly synthesized collagen, but its primary site of action in producing cleft palate is unknown. In this study time-mated Sprague-Dawley rats were given a single oral dose of 600 mg/kg BAPN at five known gestational ages in the 48 hours before palatal shelf elevation, and the fetuses were studied on days 16, 17 and 18. Evaluation of craniofacial relations and palate development in BAPN-treated heads revealed that delayed palatal shelf elevation and resulting cleft palate were related to retrognathia of the mandible. However, shortening of the mandible was due primarily to vertical and lateral bending of Meckel's cartilage. High and retruded tongue positions that were present with the deformities in Meckel's cartilage interfered with palatal shelf movement to the horizontal plane. The group treated with BAPN at 15 days 7 hours, approximately 24 hours before normal palatal shelf elevation, had the most severe defects in Meckel's cartilage, the longest delay in palatal shelf elevation and the highest incidence of cleft palate. Inhibition of crosslinking of collagen in Meckel's cartilage appeared to weaken the cartilage during the critical period in facial development when extention of the tongue and mandible beneath the primary palate is required to facilitate palatal shelf elevation.

Aminopropionitrile↗

PubMed2000

Temporospatial distribution of matrix metalloproteinase and tissue inhibitors of matrix metalloproteinases during murine secondary palate morphogenesis.

Extracellular matrix (ECM) molecules are known to play a pivotal role in the morphogenesis of the secondary palate. The maintenance and degradation of the ECM is mediated in part by the matrix metalloproteinases (MMPs) and their endogenous inhibitors TIMPs. MMPs and TIMPs have previously been shown to be developmentally regulated within the palatal shelf during secondary palate morphogenesis. This study was conducted to examine the temporospatial distribution of these enzymes and their inhibitors within the palatal shelves using immunofluorescent localization to determine if specific changes occur in their distribution concomitant with events in palatal shelf formation and reorientation. Frontal sections through the posterior palatal shelves at gestational day (gd) 12, 13 and 14 were immunofluorescently stained for MMPs 2, 3, 9, and 13 and TIMPs 1, 2, and 3 using standard protocols and commercially available antibodies. The results demonstrated that MMPs and TIMPs were already present within the palatal shelf mesenchyme 30 h prior to reorientation and closure and that their expression within the shelf mesenchyme increased as the shelves remodeled, then decreased with closure and fusion. Increased distribution of MMPs and TIMPs within specific regions of the palatal mesenchyme and palatal epithelial basement membrane preceded decreases previously observed within these areas for their substrates, fibronectin, collagen III and collagen I. In addition, MMP-3 and TIMP-3 were immunolocalized to regions of the palatal epithelium that undergo reorganization concomitant with reorientation. The results of this study indicate that MMPs and TIMPs are developmentally regulated during palatal shelf morphogenesis and that their distribution correlates with the distribution of the ECM components of the palatal shelf they regulate. These results provide support for the idea that temporospatially controlled interactions between MMPs and their substrates may be pivotal in modulating events in palatal morphogenesis.

Animals↗

PubMed1999

The fetal cleft palate: II. Scarless healing after in utero repair of a congenital model.

The role of fetal surgery in the treatment of non-life-threatening congenital anomalies remains a source of much debate. Before such undertakings can be justified, models must be established that closely resemble the respective human anomalies, and the feasibility and safety of these in utero procedures must be demonstrated. The authors recently described and characterized a congenital model of cleft palate in the goat. The present work demonstrates the methodology they developed to successfully repair these congenital cleft palates in utero, and it shows palatal healing and development after repair. A surgically created cleft model was developed for comparative purposes. Palatal shelf closure normally occurs at approximately day 38 of gestation in the caprine species. Six pregnant goats were gavaged twice daily during gestational days 32 to 41 (term, 145 days) with a plant slurry of Nicotiana glauca containing the piperidine alkaloid anabasine; the 12 fetuses had complete congenital clefts of the secondary palate. Repair of the congenital clefts was performed at 85 days of gestation using a modified von Langenbeck technique employing lateral relaxing incisions with elevation and midline approximation of full-thickness, bilateral, mucoperiosteal palatal flaps followed by single-layer closure. Six congenitally clefted fetuses underwent in utero repair, six remained as unrepaired controls. Twelve normal fetuses underwent surgical cleft creation by excision of a 20 x 3 mm full-thickness midline section of the secondary palate extending from the alveolus to the uvula, at 85 days of gestation. Six surgically clefted fetuses underwent concurrent repair of the cleft at that time; six clefted fetuses remained as unrepaired controls. At 2 weeks of age, no congenitally or surgically created clefts repaired in utero demonstrated gross or histologic evidence of scar formation. A slight indentation at the site of repair was the only remaining evidence of a cleft. At 6 months of age, normal palatal architecture, including that of mucosal, muscular, and glandular elements, was seen grossly and histologically. Cross-section through the mid-portion of the repaired congenitally clefted palates demonstrated reconstitution of a bilaminar palate, with distinct oral and nasal mucosal layers, after single-layer repair. In utero cleft palate repair is technically feasible and results in scarless healing of the mucoperiosteum and velum. The present work represents the first in utero repair of a congenital cleft palate model in any species. The use of a congenital cleft palate model that can be consistently reproduced with high predictability and little variation represents the ideal experimental situation. It provides an opportunity to manipulate specific variables, assess the influence of each change on the outcome and, subsequently, extrapolate such findings to the clinical arena with a greater degree of relevance.

Animals↗

PubMed1998

Deformation of the palate in preterm infants.

AIM: To investigate the effect of gestation, postmenstrual age, and orotracheal intubation on palate morphology. METHODS: A prospective study was made of 76 newborn infants of 25 to 41 weeks' gestation. Palate dimensions were measured on plaster models produced from serial palatal impressions. Palate size relative to that of the mouth was assessed using a ratio of palate depth to palate width (Palatal Index). RESULTS: Palate depth and width were related to postmenstrual age and gestation. Palatal Index ranged from 0.15 to 0.57, indicating a wide variation in palate shape, but gestation and postmenstrual age had no effect. Prolonged intubation had a small effect, equivalent to an increase in palatal depth of less than 2 mm at 32 weeks' postmenstrual age. The effect was transient. CONCLUSION: Prolonged orotracheal intubation (> 10 days) leads to a small and temporary increase in palatal depth. However, this is unlikely to account for palatal grooving, which is probably caused by an overgrowth of the lateral palatine ridges.

Anthropometry↗

PubMed2006

A mutation in RYK is a genetic factor for nonsyndromic cleft lip and palate.

OBJECTIVE: The RYK, EPHB2, and EPHB3 genes are attractive candidates for cleft lip and/or palate and cleft palate only pathogenesis. Both the Ryk-deficient mouse and Ephb2/Ephb3 (genes for interaction molecules with RYK) double-mutant mouse show cleft palate. SETTING: Mutation searches for RYK, EPHB2, and EPHB3 were carried out in a large number of Japanese and Vietnamese patients with cleft lip and/or palate and cleft palate only. Case-control study and transmission disequilibrium tests were performed also, using three single nucleotide polymorphisms within a linkage disequilibrium block in RYK. Seven haplotypes were constructed from the single nucleotide polymorphisms. RESULTS: A missense mutation, 1355G>A (Y452C), in RYK was identified in one Vietnamese patient with cleft lip and/or palate. This mutation was not found among 1646 Vietnamese, Japanese, and Caucasians, including 354 cleft lip and/ or palate and cleft palate only patients. Colony formation assay using NIH3T3 cells transfected with mutant cDNA revealed that mutant RYK had significantly reduced protein activity, compared with those with wild-type RYK, implying that the transformation ability of RYK is depleted by this mutation. Although a case-control study and transmission disequilibrium tests on three individual single nucleotide polymorphisms provided no evidence for association with oral clefts, a case-control study on one rare haplotype suggested a positive association in Japanese patients with cleft lip and/or palate and cleft palate only. No mutations in EPHB2 and EPHB3 were found in any patients examined. CONCLUSION: The findings suggested that a missense mutation, 1355G>A, and one rare single nucleotide polymorphisms haplotype may play a role in the development of cleft lip and/or palate in the Vietnamese, and cleft lip and/ or palate and cleft palate only in the Japanese.

3T3 Cells↗

PubMed2002

Frequency of pharyngoplasty after primary repair of cleft palate.

BACKGROUND: The frequency of pharyngoplasty after initial repair of cleft palate is a direct measure of the success or failure of the primary palatal repair with respect to velopharyngeal function. The optimal timing and surgical technique for the repair of cleft palate remain subjects of debate. PURPOSE: To assess the outcome of various techniques for primary palatal repair, specifically the frequency of secondary pharyngoplasty, and to determine the significance, if any, of certain variables to this outcome. METHODS: A pool of 114 patients with cleft lip and palate was compiled from a retrospective analysis of medical records for more than 300 consecutive patients treated over a 15-year period (1980-1995). The review included only patients who had been treated by the same surgeon or by his resident. A 1-stage palatal repair was performed on all patients, in which the hard and the soft palate were closed simultaneously. The following data were collected: patient's sex, patient's date of birth, type of cleft, technique used for initial repair, age at initial repair and date of secondary pharyngoplasty surgery, if performed. RESULTS: The overall frequency of subsequent pharyngoplasty was 25% (28 patients). The rate of secondary surgery was significantly higher for boys (21/63 or 33%) than for girls (7/51 or 14%). There were also significant differences in the rate of secondary pharyngoplasty according to type of cleft: 50% (6/12) for patients with bilateral cleft lip and palate, 44% (7/16) for those with hard and soft cleft palate, 21% (8/38) for those with unilateral cleft lip and palate, 20% (3/15) for those with submucous cleft palate and 12% (4/33) for those with soft cleft palate. Surgical technique for the primary repair (V-Y pushback or von Langenbeck procedure) was not a significant factor in determining the rate of subsequent pharyngoplasty, nor was age at primary repair, although those who underwent primary repair at age 12-14 months were least likely to require pharyngoplasty. CONCLUSION: In this study the frequency of velopharyngeal insufficiency after 1-stage palatoplasty was consistent with previously reported results. Of interest would be a comparison of 1-stage and 2-stage approaches to primary palate repair in young patients.

Age Factors↗

PubMed1981

Presence of serotonin in the palate just prior to shelf elevation.

Since serotonin and its antagonists affect shelf rotation in mouse embryo culture, experiments were carried out to determine whether a serotonergic system is present in the palate. Employing [3H]5-HT, day-14.5 embryos incorporated the monoamine into palates. Active uptake of [3H]5-HT was shown since excised palates incorporated 9-fold more radioactivity at 37 degrees C than at 4 degrees C. Synthesis of palatal serotonin was measured. Embryos were cultured in the presence of the serotonin precursor, [3H]5-HTP, and radioactive 5-HT was monitored in the palate by thin-layer chromatography. Furthermore, excised palates were incubated with [3H]5-HTP and radioactive 5-HT was measured. Incorporation was linear for about 6 h. In addition, another radioactive compound was detected which had the same Rf as the methylated derivative, 5-methoxytryptamine. Synthesis of this compound was appreciable, about 30% of that of serotonin. Levels of serotonin in the palate were measured by high pressure liquid chromatography. Palates at day 14.5 of gestation contained 0.40 ng serotonin/mg protein, which was greater than that of tongue (0.33), body (0.14) but less than that of brain (3.09). Serotonin in palate and other embryonic tissues increased with time of development. Dopamine levels in the palate and other tissues were also determined. The distribution of serotonin in the palate was analyzed by culturing day-14.5 embryos in the presence of [3H]5-HTP, and after aldehyde fixation, paraffin embedment and sectioning, autoradiography was performed. Grains were observed throughout the palate in cells of regions 2 and 3, internal mesenchyme, tooth germ, and epithelium. Surprisingly, the pterygopalatine nerve, maxillary nerve and pterygopalatine ganglion contained an appreciable concentration of grains. Thus, the presence of serotonin in the palate is consistent with the neurotransmitter playing a role in shelf elevation.

Animals↗

PubMed1980

Palate morphogenesis. V. Effects of cholinergic agonists and antagonists on rotation in embryo culture.

Morphological studies have shown that the pterygopalatine ganglion in the day-14.5 mouse palatal shelf lies adjacent to the putative contractile system of region-2 cells in the posterior palate. It is of interest to learn whether the ganglion could influence rotation of the palate. Results of embryo culture experiments showed that acetylcholine appeared to play a role in posterior shelf rotation since cholinergic agents (pyridostigmine, bethanechol and carbachol) stimulated elevation of that end of the palate. To characterize the putative receptors mediating the effects of the cholinergic agonists on palate shelf elevation, muscarinic or nicotinic antagonists were introduced into the emrbyo culture system. Atropine, a muscarinic blocking agent, did not produce any significant effect on palate shelf rotation when tested in overnight and 2 h embryo cultures at 3 X 10(-5) M and 10(-4) M, respectively. Neither did atropine inhibit significantly the stimulation produced by 10(-8) M bethanechol, Thus, the cholinergic effect was probably not on muscarinic receptors of the contractile system. However, hexamethonium, a nicotinic antagonist, at 10(-6) M and 10(-4) M profoundly inhibited posterior shelf rotation to about 35% of the control value in a 2 h incubation. In addition, 10(-4) M hexamethonium inhibited posterior palate rotation to 11% of the control value after overnight culture. Furthermore, hexamethonium was able to reverse the stimulation of posterior rotation produced by carbachol. Partial inhibition of palate rotation by hexamethonium was also demonstrated when pregnant dams were injected with drug at doses approximately corresponding to 10(-6) and 10(-4) M. Hexamethonium treatment resulted in approximately 30% of the palates not completely rotated at day 15.5 compared to only 9.3% in the control. Hexamethoniuim also produced a significant increase in the palate gap and a comparable decrease in palate fusion. These effects were slightly greater at the posterior end of the palate. Thus, the cholinergic ganglion in the posterior palate may play a role in regulating shelf rotation at that end through a nicotinic pathway.

Acetylcholinesterase↗

PubMedDate not supplied

Mesenchymal changes associated with retinoic acid induced cleft palate in CD-1 mice.

Retinoic acid (RA) is teratogenic in many species and is an effective inducer of cleft palate in mice. The pathogenesis of cleft formation varies with the timing of exposure. It has been demonstrated, before formation of the palatal shelves, that RA exposure results in insufficient mesenchymal tissue, and palatal shelves fail to make contact. However, at the palatal shelf outgrowth stage, RA exposure affects shelf elevation and growth in rats, and possibly medial edge epithelium (MEE) differentiation in mice. The objective of this study was to examine the morphologic and functional changes associated with cleft formation in mice following exposure during shelf outgrowth. Particular emphasis was placed on evaluating the timing of palatal shelf elevation in RA exposed embryos and on identifying differentiation events occurring concurrently in the epithelium. On gestational day (GD) 12 (8:00 AM), gravid CD-1 mice were gavaged with 70 mg/kg RA or vehicle. This protocol produced a 100% incidence of cleft palate at term, allowing us to correlate the morphological and/or biochemical changes observed at pre-fusion time points. Embryos were collected at 12 hr intervals through GD 15, beginning 4 hr after exposure. Serial sections of embryos were either stained with H&E, with a battery of lectins [Sambucus nigra (SNA), Arachis hypogaea (PNA), Ricinus communis (RCA-1), Glycine max (SBA), Succinylated Wheat Germ (S-WGA)], or with a probe to hyaluronan. Throughout the period of normal palate development, the shelf mesenchyme showed increasing regional organization and progressive hydration and these changes were correlated with increase Hyaluronan (HA) deposition. RA treatment resulted in lose of regional organization and delayed mesenchyme hydration. In association with these changes there were reductions in HA deposition and extracellular matrix glycoconjugates recognized by PNA in the palate mesenchyme. Further there was a considerable delay in palatal shelf elevation and palate shelf did not make contact at the midline. Our data indicates, in embryos exposed on GD 12 to levels of RA sufficient to induce a 100% incidence of clefting, that cleft formation is a result of palatal shelves failing to make contact. Alterations in mesenchyme development and the subsequent delay in palate shelve elevation are central to RA-induced cleft formation following exposure at the palate shelf out growth stage.

Animals↗

PubMed2004

Palatability: response to nutritional need or need-free stimulation of appetite?

The traditional view of palatability was that it reflected some underlying nutritional deficit and was part of a homeostatically driven motivational system. However, this idea does not fit with the common observation that palatability can lead to short-term overconsumption. Here, we attempt to re-evaluate the basis of palatability, first by reviewing the role of salt-need both in the expression of liking for salty tastes, and paradoxically, in dissociating need from palatability, and second by examining the role of palatability in short-term control of appetite. Despite the clarity of this system in animals, however, most salt (NaCl) intake in man occurs in a need-free state. Similar conclusions can be drawn in relation to the palatability of food in general. Importantly, the neural systems underlying the hedonic system relating to palatability and homeostatic controls of eating are separate, involving distinct brain structures and neurochemicals. If palatability was a component of homeostatic control, reducing need-state should reduce palatability. However, this is not so, and if anything palatability exerts a stronger stimulatory effect on eating when sated, and over-consumption induced by palatability may contribute to obesity. Differential responsivity to palatability may be a component of the obese phenotype, perhaps through sensitisation of the neural structures related to hedonic aspects of eating. Together, these disparate data clearly indicate that palatability is not a simple reflection of need state, but acts to promote intake through a distinct hedonic system, which has inputs from a variety of other systems, including those regulating need. This conclusion leads to the possibility of novel therapies for obesity based on modulation of hedonic rather than homeostatic controls. Potential developments are discussed.

Appetite Regulation↗

PubMed2003

Nonneuronal expression of the GABA(A) beta3 subunit gene is required for normal palate development in mice.

Cleft palate is one of the most common birth defects in humans, in which both genetic and environmental factors are involved. In mice, loss of the GABA(A) receptor beta3 subunit gene (Gabrb3) or the targeted mutagenesis of the GABA synthetic enzyme (Gad1) leads to cleft palate. These observations indicate that a GABAergic system is important in normal palate development. To determine what cell types, neuronal or nonneuronal, are critical for GABA signaling in palate development, we used the neuron-specific enolase promoter to express the beta3 subunit in Gabrb3 mutant mice. Expression of this construct was able to rescue the neurological phenotype, but not the cleft palate phenotype. Combined with the previous observation demonstrating that ubiquitous expression of the beta3 subunit rescued the cleft palate phenotype, a nonneuronal GABAergic system is implicated in palate development. Using immunohistochemistry, we detected GABA in the developing palate, initially in the nasal aspect of palatal epithelium of the vertical shelves; later in the medial edge epithelium of the horizontally oriented palatal shelves and in the epithelial seam during fusion. Based on these observations, we propose that GABA, synthesized by the palatal epithelium, acts as a signaling molecule during orientation and fusion of the palate shelves.

Animals↗

PubMed2002

TGF-beta(3)-induced chondroitin sulphate proteoglycan mediates palatal shelf adhesion.

In mammals, the adhesion and fusion of the palatal shelves are essential mechanisms in the development of the secondary palate. Failure of any of these processes leads to the formation of cleft palate. The mechanisms underlying palatal shelf adhesion are poorly understood, although the presence of filopodia on the apical surfaces of the superficial medial edge epithelial (MEE) cells seems to play an important role in the adhesion of the opposing MEE. We demonstrate here the appearance of chondroitin sulphate proteoglycan (CSPG) on the apical surface of MEE cells only immediately prior to contact between the palatal shelves. This apical CSPG has a functional role in palatal shelf adhesion, as either the alteration of CSPG synthesis by beta-D-Xyloside or its specific digestion by chondroitinase AC strikingly alters the in vitro adhesion of palatal shelves. We also demonstrate the absence of this apical CSPG in the clefted palates of transforming growth factor beta 3 (TGF-beta(3)) null mutant mice, and its induction, together with palatal shelf adhesion, when TGF-beta(3) is added to TGF-beta(3) null mutant palatal shelves in culture. When chick palatal shelves (that do not adherein vivo nor express TGF-beta(3), nor CSPG in the MEE) are cultured in vitro, they do not express CSPG and partially adhere, but when TGF-beta(3) is added to the media, they express CSPG and their adhesion increases strikingly. We therefore conclude that the expression of CSPG on the apical surface of MEE cells is a key factor in palatal shelf adhesion and that this expression is regulated by TGF-beta(3).

Animals↗