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Palatability and the micro-structure of feeding in humans: the appetizer effect.

The effects of manipulated palatability on eating were assessed in 54 human volunteers eating pasta with a tomato sauce, with palatability adjusted by the addition of three levels of oregano. Meals were divided into 2 min eating episodes separated by brief pauses during which subjects rated aspects of appetite. Both intake and eating rate were greatest in the most palatable condition (0.27% oregano), whereas the addition of 0.54% reduced intake and eating rate. Hunger ratings increased during the initial stages of the meal with 0.27% oregano, but fell throughout the meal in the other conditions, whereas fullness ratings increased similarly in all three conditions. Rated food attractiveness was greatest with 0.27% oregano, and least with 0.54% oregano, but declined similarly through the meal with all three foods. Initial ratings of palatability were similar to those for food attractiveness, but changes in palatability across meals varied between subjects. Male subjects consistently ate more and faster than females, but similar effects of manipulated palatability on intake and subjective appetite were seen in both sexes. These data are consistent with the idea that palatability increases intake through a positive-feedback reward mechanism, and offers a novel method for measuring these effects.

Adolescent↗

Dental anomalies as a microsymptom of palatal canine displacement.

AIM: A retrospective study was performed to investigate whether palatal canine displacement is associated with other dental features permitting early clinical diagnosis of the eruption disturbance. PATIENTS AND METHODS: The study was based on the complete records of 235/8556 patients at the Department of Orthodontics, School of Dental Medicine, University of Freiburg i.Br. (mean age = 14.11 years) with at least one palatally displaced permanent canine. These patients were examined for ten different morphologic parameters, e.g. impaction and congenital absence of further teeth, hypoplastic, peg-shaped, rotated and congenitally missing upper lateral incisors, supernumerary teeth, Angle classification, and cover-bite (= "Deckbiss"). The data were compared with those of a control sample of the same size with physiologic upper canine eruption (mean-age = 10.0 years). Furthermore, in a right/left comparison the local influence of anomalies of the upper lateral incisors on palatal canine displacement was evaluated by multiple linear regression analysis. RESULTS: The statistical analyses revealed that the risk of palatal canine displacement was significantly higher in patients with hypoplasia, peg shape or congenital aplasia of upper lateral incisors, further impacted and congenitally missing teeth and cover-bite. The intergroup differences in terms of gender, rotation of upper lateral incisors and Angle classification were not statistically significant. The right/left comparison revealed a significantly higher risk of palatal canine displacement in association with an adjacent hypoplastic or peg-shaped lateral incisor and with aplasia of the contralateral upper incisor. CONCLUSION: The clinical significance of the study is that the occurrence of palatally displaced canines is often closely linked with other dental anomalies. In this context, anomalies of upper lateral incisors, aplasia or impaction of further teeth, and the anomaly of cover-bite may serve as indicators of palatal canine displacement. A retarded development of the upper lateral incisor seems to be more disturbing for physiologic canine eruption than aplasia. In patients exhibiting the stated microsymptoms, close clinical follow-up of the maxillary permanent canine eruption during the late exfoliation period is strongly recommended.

Adolescent↗

Chronic prevention of mu-opioid receptor (MOR) G-protein coupling in the pontine parabrachial nucleus persistently decreases consumption of standard but not palatable food.

RATIONALE: Acute pharmacological studies implicate mu-opioid receptors (MORs) in the parabrachial nucleus (PBN) of the brainstem in modulating eating. The long-term effects of preventing the cellular function of parabrachial MORs on food consumption remain to be elucidated. OBJECTIVES: To determine whether (1) chronic inhibition of MOR-mediated G-protein coupling in the PBN of rats would persistently reduce eating and (2) food properties dictate the effects of MOR blockade. MATERIALS AND METHODS: We microinfused the irreversible MOR antagonist, beta-funaltrexamine (beta-FNA) into the lateral PBN and measured the intake of standard and calorically dense palatable chow for 1 week. First, rats were given standard chow for 20 h daily and a calorically dense palatable chow for 4 h during the day. We infused the agonist, [D: -Ala(2), N-Me-Phe(4), Glycinol(5)]-Enkephalin (DAMGO), 1 week after beta-FNA to probe the acute effects of exogenous stimulation of MORs on palatable food intake. [(35)S]GTPgammaS autoradiography quantified regional loss of MOR cellular function. Next, we measured the actions of beta-FNA on food intake in rats given only standard or palatable chow for 1 week. RESULTS: One infusion of beta-FNA persistently decreased consumption of standard but not palatable chow, regardless of feeding regimen. beta-FNA also blocked DAMGO-stimulated palatable chow intake, prevented DAMGO-stimulated G-protein coupling in the central and external lateral subnuclei of the PBN, and decreased coupling in the medial PBN. beta-FNA did not affect kappa-opioid receptors. CONCLUSIONS: MORs in the lateral PBN serve a physiological role in stimulating consumption of standard food. Properties of the diet, such as high palatability or caloric density, may override the influence of inhibiting MOR function.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Palatable daily meals entrain anticipatory activity rhythms in free-feeding rats: dependence on meal size and nutrient content.

Circadian wheel-running rhythms were monitored continuously in 3 groups of female Sprague-Dawley rats under different palatable food availability schedules. All rats had free access to standard rat chow and water throughout the study. In addition, Group 1 rats received a palatable nutrient-rich mash for 2 hr each day for 28 days, beginning 3 hr after light onset of a 12:12 LD cycle. Group 2 rats received the same mash but were limited to 4 g daily. Group 3 rats received a palatable non-nutritive mash. Ten of 13 Group 1 rats, 2 of 13 Group 2 rats, and 0 of 13 Group 3 rats showed anticipatory running prior to the daily palatable meal. Palatable mash intake was generally lower among Group 3 rats than among Group 1 rats. However, several Group 3 rats consumed non-nutritive mash in amounts which equalled or exceeded the nutritive mash intake of Group 1 rats showing anticipatory running. The results indicate that temporally limited daily access to a palatable food can entrain anticipatory wheel-running in rats that are not food-deprived. They also indicate that entrainment to periodic food availability depends on stimuli associated with the concentrated intake of nutrients rather than on the absolute size or palatability of a meal.

Animals↗

Why a palatability construct is needed.

Palatability is a hypothetical construct which is needed to account for the hedonic aspects of the taste, smell, flavour, texture, etc. of food. Palatability is influenced by innate factors, but can also be modified by learning. Powerful preferences and aversions can be conditioned by the aftereffects of food ingestion. Despite the common assertion that palatability is enhanced in a state of relative food deprivation, there is evidence to suggest that hunger and palatability act largely independently to determine intake. Accordingly a distinction should be made between the pleasantness of the taste of food (influenced by palatability) and the pleasantness of ingesting that food (influenced by hunger/satiety). Increased palatability appears to be at least part of the explanation of why certain diets promote hyperphagia and obesity. However, the postingestive effects which contribute to the greater palatability of such diets remain to be identified.

Appetite↗

Independent effects of diet palatability and fat content on bout size and daily intake in rats.

Although considerable evidence attests to the hyperphagic effects of high-fat (HF) diets, the attribute(s) of these diets (e.g., palatability, caloric density, and postingestive effects) which promote overeating is still unclear. The present studies investigated the independent effects of diet palatability and macronutrient composition on intake using the self-regulated intragastric infusion paradigm. In Experiment 1, rats were infused with either HF or high-carbohydrate (HC) diet while drinking either saccharin (Sacc) or a more palatable saccharin-glucose (SaccGlu) test solution for 9 days. HF elicited greater daily intake than HC; lick pattern analysis revealed that HF produced larger but not more frequent bouts. Test solution was not related to intake, possibly due to the relatively modest palatability manipulation. Experiment 2 provided a more sensitive test: The palatability manipulation was strengthened and diet infusion made optional by provision of chow. HF again elicited larger bout size and total daily intake (diet+chow) than HC. Rats given the more palatable solution significantly increased intake (via larger bouts) and thus the amount of diet infused, but chow intake decreased such that total kilocalorie intake was not significantly related to solution palatability. The reliable observation that HF promoted larger bout size and greater total kilocalorie intake than HC provides additional evidence that fat sends weaker feedback signals relevant to controls of both satiation (suppression of ongoing eating, behaviorally manifest in meal size) and satiety (suppression of subsequent intake, reflected in total daily intake).

Analysis of Variance↗

Test-meal palatability alters the effects of intragastric fat but not carbohydrate preloads on intake and rated appetite in healthy volunteers.

Manipulations of test meal palatability and nutritional need-state to examine feeding behaviour have, to date, been studied in isolation. Recent investigations have attempted to examine these influences in combination. In the present study, healthy young males received intragastric infusions of soup (265 or 1514 kJ) on four different occasions. The infusion was shortly followed by a meal varying in its palatability (PALATABLE or BLAND). The effect of macronutrient type (CHO or Fat) in the high-energy preloads was also examined in a between-subject manner. High CHO preloads significantly decreased test meal intake and this decrease was unaffected by meal palatability. High fat preloads did not significantly reduce test meal intake. Additionally, more food was consumed following high fat preloads when the test meal was PALATABLE. Within-meal ratings of appetite revealed that hunger was diminished to a greater extent by CHO than by Fat preloads. Appetite was stimulated by the PALATABLE meal to a greater extent in the group receiving Fat than in those receiving the CHO preload. Comparison with a similar oral preloading study revealed differences that suggest possible interactions between cognitive, oro-sensory and gastric controls of feeding when palatable foods are consumed.

Adult↗

Children with Down Syndrome: oral development and morphology after use of palatal plates between 6 and 18 months of age.

OBJECTIVES: The aim of this study was to describe oral development and morphology in 18-month-old children with Down syndrome (DS) treated with palatal plates in combination with structured communication and speech training. The aim is further to describe the design of the palatal plates, compliance in their use and to give a brief report of their effect on oral motor function and speech. SAMPLE AND METHODS: Forty-two children with DS were followed from < or = 6 months of age until 18+/-3 months old. In addition to language intervention, and oral motor and sensory stimulation provided by speech therapists for all children with DS in Sweden, palatal plates provided by dentists are included in the training programme. In the evaluation, the children in the project were compared with two control groups of children matched for age; one group of children with DS who had not been treated with palatal plates, and one group of children with normal development. RESULTS: Compared to the children with normal development, both groups of children with DS had fewer teeth erupted and a lower prevalence of sucking habits. Deviant morphology of the tongue in the form of diastase, lingua plicata or a sulcus in the anterior third of the tongue was only seen in children with DS. All children with normal development had positive values for overjet compared to 53% of the children with DS. The palatal plates were used 2-3 times daily for a total mean time of 15 min. Compliance in use of the plates decreased with age, mainly due to eruption of teeth and subsequent loss of retention. Evaluation of oral motor function and speech show that the children with DS in the project had better motor prerequisites for articulation than the control children with DS. CONCLUSION: Palatal plate therapy did not affect oral parameters, i.e., eruption of teeth, types and prevalence of sucking habits, tongue morphology and symptoms of hypotonia. In combination with oral motor and sensory stimulation, palatal plate therapy had a positive effect on oral motor performance and prerequisites for articulation.

Case-Control Studies↗

Use of the Pala-nate device in the prevention of palatal grooves in premature, intubated infants.

OBJECTIVE: Previous studies demonstrated that the use of a custom-made intraoral acrylic appliance, known as a palatal stabilizing device, prevents palatal groove formation and reduces the frequency rate of accidental extubations in premature, intubated babies. In this study, we compared the effectiveness of a prefabricated palatal device with an acrylic custom-made palatal stabilizing device. Specifically, we compared the stability, fit, and retention of these two devices. DESIGN: Randomized comparative study. SETTING: Clincal trial. PATIENTS: A total of 70 medically stable, premature, intubated babies. INTERVENTIONS: A total of 70 medically stable, premature, intubated babies randomly received Pala-nate (experimental group, n = 34) or palatal stabilizing device (control group, n = 36). MEASUREMENTS AND MAIN RESULTS: Differences among birth weight, gestational age, and period of intubation of the two groups were statistically nonsignificant at p </=.05. Although both appliances were effective in the prevention of palatal grooves, the Pala-nate was less retentive, thus requiring greater monitoring, and it was associated with a larger number of accidental extubations. The differences between the two groups were statistically significant at p </=.05. CONCLUSIONS: We concluded that the custom-made, acrylic, palatal stabilizing device was more stable and more effective in the prevention of spontaneous extubations in premature orally intubated infants.

Journal Article↗

Children with Down syndrome: oral development and morphology after use of palatal plates between 6 and 48 months of age.

OBJECTIVE: The aim of this study was to describe the number of erupted teeth, sucking habits, tongue morphology, facial expression and speech in children with Down syndrome (DS) aged 48 +/- 6 months and treated from 6 months of age with palatal plates in combination with speech and language therapy. METHODS: The research took the form of a multicentre, multidisciplinary, longitudinal study of children with DS followed from the age of 6 months. A total of 37 children with DS were included. One child could not cooperate at all and was excluded from the evaluations. In combination with speech and language intervention provided by speech and language therapists, the children used palatal plates provided by dentists from 6 months of age. In the evaluation, the children in the sample (n = 36) were compared with two similarly aged control groups: one group of children with DS who never had used palatal plates (n = 31) and one group of children with normal development (n = 36). The evaluation of oral parameters was performed by dentists after calibration. Registration of facial expression and speech was done by a speech and language therapist, and the evaluation was done by two speech and language therapists and one phonetician who were calibrated in joint discussions. RESULTS: In contrast to the children with DS in the control group, the subjects in the study were found to have as many erupted teeth as the children with normal development. The prevalence of sucking habits did not differ between the three groups. Only children with DS sucked their tongue, a toy or other things in addition to a thumb or dummy. The prevalence of tongue diastase in the study group with DS was of the same magnitude as in the evaluation at the age of 18 +/- 3 months. The palatal plates were used by 57-65% of the children without any larger problems. In the study sample, the possible beneficial effects of palatal plate therapy were a lower prevalence of posterior cross-bite, a higher prevalence of frontal cusp-to-cusp relation and a lower prevalence of frontal open bite. Evaluation of facial expression and speech showed a higher score for facial expression and a better communicative capacity in the children in the study group than in the control children with DS. CONCLUSIONS: In children with DS, palatal plate therapy between 6 and 48 months of age in connection with speech and language intervention had a positive effect on occlusion, oral motor function, facial expression and speech. No harmful effects were observed. Although this is a valuable method, however, it must be emphasized that palatal plate therapy puts additional demands on already burdened children and their caretakers.

Case-Control Studies↗

A daily palatable meal without food deprivation entrains the suprachiasmatic nucleus of rats.

Food is considered a potent Zeitgeber for peripheral oscillators but not for the suprachiasmatic nucleus (SCN), which is entrained principally by the light-dark cycle. However, when food attains relevant properties in quantity and quality, it can be a potent Zeitgeber even for the SCN. Here we evaluated the entrainment influence of a daily palatable meal, without regular food deprivation, on the circadian rhythm of locomotor activity and the c-Fos and PER-1 protein expression in the SCN. Rats fed ad libitum, in constant darkness, received a palatable meal for 6 weeks starting in the middle of the subjective day. Locomotor activity showed entrainment when the offset of activity coincided with the palatable meal-time. In the SCN, the peak expression of c-Fos was observed at palatable meal-time and PER-1 showed a peak during the onset of subjective night, as predicted according to the behavioural entrained pattern. In addition, c-Fos and PER-1 expression in the paraventricular thalamic nucleus (PVT) showed increased expression at palatable meal-time, while the intergeniculate leaflet did not, suggesting that the PVT may be involved as an input pathway of palatable food-entrainment to the SCN. These results demonstrate that daily access to a palatable meal can entrain the SCN; several stimuli can be implicated in this process, including motivation and arousal.

Animals↗

Contrast effect in evaluating palatability of beverages.

This study aimed to clarify the contextual effect in evaluation of the pleasantness of beverages. Participants were presented a test stimulus and were then asked to rate how much they liked it before and after presentation of a contextual stimulus. Specifically, after participants were exposed to a less palatable beverage, they evaluated the test beverage as being more palatable than when their judgment of a test drink occurred after presentation of a neutral or palatable beverage (a positive contrast effect). This contextual effect can be explained by the reasoning that participants were affectively adapted to the palatability (less palatable) of a less palatable stimulus after repeated exposure; thus, they evaluated the test stimulus as more palatable. This study suggests that the evaluated value of the contextual stimuli affects evaluation of the test stimulus. The authors also suggest that these context effects are probably found in everyday life.

Adult↗

A morphological and histochemical study of the developing tongue musculature in the mouse: its relationship to palatal closure.

Some question exists concerning the ability of the embryonic tongue to undergo reflex movements at the time of palatal closure (15.5 days of development). Functional motor endplates are prerequisite for such movements to occur. Light and ultrastructural cytochemical methods were employed to elucidate the morphology of neuromuscular relationships in the developing mouse tongue. The A/Jax mice used in the experiments demonstrated a 12-20% incidence (seasonal variation) of spontaneous cleft palate, allowing a correlation between normal and teratological processes. Organized myofibrils were first seen in tongues of normal and spontaneous cleft lip-cleft palate (SCL-CP) specimens at 14.5 days of development. The thiocholine technique of Karnovsky and Roots was used to demonstrate acetylcholinesterase (AChE) activity at the light microscope level. The Lewis and Schute method was used for ultrastructural localization of this enzyme. Tissues from normal and SCL-CP specimens from 12.5 to 20.5 days of gestation failed to show differences in amounts or distribution of AChE activity. AChE activity was seen as early as 14 day's gestation. Electron microscopic studies demonstrated reaction product in the endoplasmic reticulum and nuclear envelope of developing myoblasts. AChE activity at the developing neuromuscular junction and the occurrence of myofilaments preceded palatal closure by several days. Based on these morphological and histochemical findings the tongue of normal and SCL-CP embryos appears capable of responding to a neurogenic stimulus at the time of palatal closure. The findings suggest that the tongue of animals exhibiting a spontaneous cleft palate is not actively involved in the etiology of this condition.

Acetylcholinesterase↗

Ultrastructural and cytochemical observations on 5-fluorouracil-induced cleft-palate development in hamster.

Sequential alterations in 5-fluorouracil-treated hamster fetal palate were studied by light and electron microscopy and by acid phosphatase cytochemistry. At an early stage in 5-fluorouracil-treated fetuses, when the palatal shelves were vertical, lysosomes first appeared in cells of the prospective fusion epithelium and then in the cells of subjacent mesenchyme. In contrast to controls, increasing numbers of both the epithelial and mesenchymal cells of the vertical palate showed lysosomal injury in 5-fluorouracil-treated fetuses as development progressed. Subsequently, the basal lamina in the vertical palate showed alterations, characterized initially by disturbances in lamina lucida, by fingerlike extensions of lamina densa, and ultimately by its complete breakdown. At a later stage, when shelves became horizontal, the lysosomes were absent in both the epithelial and mesenchymal cells, and the basal lamina continuity was restored. Unlike controls, however, 5-fluorouracil-treated horizontal shelves never contacted one another. Instead, the epithelia of the horizontal shelves underwent stratification. It appears that premature formation of lysosomes in palatal epithelial and mesenchymal cells following 5-fluorouracil treatment disrupts normal cytodifferentiation and affects the integrity of the basal lamina; both effects are associated with cleft-palate development.

Acid Phosphatase↗

In vitro activation of adenylate cyclase by parathyroid hormone and calcitonin during normal and hydrocortisone-induced cleft palate development in the golden hamster.

An adenylate cyclase highly responsive to stimulation by parathyroid hormone (PTH) and calcitonin (CT) in vitro was observed at certain times during normal prenatal development of the maxillary-palatal process complex in the golden hamster. Responses of the enzyme to these hormones were barely detectible at the earliest stage examined (day 10/20). The enzyme became extremely sensitive to activation by either hormone during the time of rapid growth of the palatal processes (day 11/20) and during fusion between the palatal processes (day 12/20). Thereafter, responses were greatly diminished and little or no activation of adenylate cyclase was observed until birth. Adenylate cyclase from fetuses in which clefts of the secondary palate were induced by maternal treatment with hydrocortisone (50 mg) on day 11/3 also displayed an enhanced sensitivity to PTH and CT on day 11/20, but the sensitivity of the enzyme was greatly decreased from that in normal animals during the normal time of palatal fusion (day 12/20) and was barely detectible or absent at the remaining time periods studied (days 13/20 and 14/20). Addition of hydrocortisone to the incubation mixture, either separately or in combination with PTH or CT, did not remarkably affect the response of adenylate cyclase to these hormones. Moreover, the appearance of the adenylate cyclase sensitive to hormonal activation did not result from changes in phosphodiesterase activity during palatal maturation.

3',5'-Cyclic-AMP Phosphodiesterases↗

Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E.

BACKGROUND: The mycotoxin, secalonic acid D (SAD), a known animal and potential human cleft palate (CP)-inducing agent, is produced by Pencillium oxalicum in corn. SAD selectively inhibits proliferation of murine embryonic palatal mesenchymal (MEPM) cells leading to a reduction in cell numbers. These effects can explain the reduction in shelf size and the resulting CP seen in the offspring of SAD-exposed mice. Ability of SAD to inhibit proliferation as well as to block the progression of cells from G1- to S-phase of the cell-cycle were also shown in the human embryonic palatal mesenchymal (HEPM) cells suggesting the potential CP-inducing effect of SAD in human beings METHODS: Gestation day (GD) 12 mouse embryos and HEPM cells were used to test the hypothesis that the cell-cycle block induced by SAD results from a disruption of stage-specific regulatory components both in vivo and in vitro. The effects of SAD on the activity of various cyclin dependent kinases (CDK) and on the levels of various positive (cyclins and CDK) and negative (CDK inhibitors p15, 16, 18, 19, 21, 27, 57) cell-cycle regulators were assessed by performing kinase assays and immunoblots, respectively. RESULTS: In the murine embryonic palates, SAD specifically inhibited G1/S-phase-specific CDK2 activity, reduced the level of cyclin E and tended to increase the level of the CIP/kip CDK inhibitor, p21. In the HEPM cell cultures, exposure to IC50 of SAD significantly affected all of the above targets. In addition, a reduction in the levels/activity of CDK 4/6, a reduction in the levels of cyclins D1, D2, D3, E, A, and all INK4 family proteins, and an increase in the level of the CIP/kip CDK inhibitor, p57, were also seen. CONCLUSIONS: These results suggest that the S-phase-specific cell-cycle proteins CDK2, cyclin E and possibly p21 are the common targets of SAD in murine palatal shelves in vivo and in human embryonic palatal mesenchymal cells in vitro and may be relevant to the pathogenesis of SAD-induced CP.

Animals↗

TGF-beta3-dependent SMAD2 phosphorylation and inhibition of MEE proliferation during palatal fusion.

Transforming growth factor (TGF) -beta3 is known to selectively regulate the disappearance of murine medial edge epithelium (MEE) during palatal fusion. Previous studies suggested that the selective function of TGF-beta3 in MEE was conducted by TGF-beta receptors. Further studies were needed to demonstrate that the TGF-beta signaling mediators were indeed expressed and phosphorylated in the MEE cells. SMAD2 and SMAD3 were both present in the MEE, whereas SMAD2 was the only one phosphorylated during palatal fusion. SMAD2 phosphorylation was temporospatially restricted to the MEE and correlated with the disappearance of the MEE. No phosphorylated SMAD2 was found in MEE in TGF-beta3(-/-) mice, although nonphosphorylated SMAD2 was present. The results suggest that TGF-beta3 is required for initiating and maintaining SMAD2 phosphorylation in MEE. Phospho-SMAD3 was not detectable in palate during normal palatal fusion. Previous results suggested TGF-beta-induced cessation of DNA synthesis in MEE cells during palatal fusion in vitro. The present results provide evidence that inhibition of MEE proliferation in vivo was controlled by endogenous TGF-beta3. The number of 5-bromo-2'-deoxyuridine (BrdU) -labeled MEE cells was significantly reduced in TGF-beta3(+/+) compared with TGF-beta3(-/-) mice when the MEE seam formed (t-test, P < 0.05). This finding suggests that TGF-beta3 is required for inhibiting MEE proliferation during palatal fusion. The inhibition of MEE proliferation may be mediated by TGF-beta3-dependent phosphorylation of SMAD2.

Animals↗

Retinoic acid-induced alterations in the expression of growth factors in embryonic mouse palatal shelves.

Retinoic acid (RA) is teratogenic in many species, producing multiple malformations, including cleft palate. The effects of RA which lead to cleft palate vary depending on the stage of development exposed. After exposure of embryonic mice to RA on gestation day (GD) 10, abnormally small palatal shelves form. After exposure on GD 12 shelves of normal size form, but fail to fuse, as the medial cells proliferate and differentiate into a nasal-like epithelium. Growth factors and their receptors play an important role in regulating development, and the expression of EGF receptors, EGF, TGF-alpha, TFG-beta 1, and TGF-beta 2 has been reported in the mouse embryo. In a variety of cell types in culture, these growth factors are capable of regulating proliferation, differentiation, expression of matrix proteins, and other cellular events including epithelial-mesenchymal transformations. The present study examines immunohistochemically the expression of EGF, TGF-alpha, TGF-beta 1, and TGF-beta 2 in the control embryonic palatal shelves from GD 12 to 15 and the effects of RA treatment on GD 10 or 12 on their expression on GD 14 and 16. These growth factors were shown to have specific temporal and spatial expression in the palatal shelf. With advancing development the levels of TGF-alpha decreased while the expression of EGF increased. TGF-beta 2 localization became regional by GD 14-15, with higher levels found in epithelial cells and chondrogenic mesenchyme. TGF-beta 1 occurred in epithelial and mesenchymal cells and distribution did not change substantially with advancing development. RA exposure altered the expression of TFG-alpha, TGF-beta 1, and TGF-beta 2, but significant effects on EGF were not found. The effects on TGF-alpha and TGF-beta 1 expression were dependent on the gestational age exposed. Levels of TGF-alpha on GD 14 decreased after RA exposure on GD 10, but increased after GD 12 exposure. TGF-beta 1 expression in the mesenchyme was increased after exposure on GD 12, but was unaffected by RA on GD 10. After exposure on either day, the levels of TGF-beta 2 increased in GD 14 nasal epithelial cells. Acting in concert, growth factors could regulate events critical to formation of the secondary palate, including cessation of medial epithelial cell proliferation, synthesis of extracellular matrix proteins in the mesenchyme, programmed cell death of medial epithelial peridermal cells, and transformation of basal epithelial medial cells to mesenchymal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗