Labeling Index and Cellular Density in Palatine Shelves of Cleft-Palate Mice

Mott, William J.; Toto, Patrick D.; Hilgers, Donald C.

doi:10.1177/00220345690480021601

Cited by 24 publications

(1 citation statement)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Utilizing whole mouse fetal heads and an unconventional method of cytosol preparation, Hackney (35) (42,43). These results are in accord with observations that dexamethasone and cortisone inhibited the in vivo proliferation of mesenchymal cells of rat and mouse palatal processes (3,44,45). This inhibition of mesenchymal cell growth is a key factor in producing glucocorticoid-induced cleft palate (14) which is mediated by a receptor-dependent mechanism, presumably involving altered transcription of a key enzyme or protein in the palate (46).…”

Section: Glucocorticoid-induced Cleft Palatesupporting

confidence: 89%

Receptor-Dependent Mechanisms of Glucocorticoid and Dioxin-Induced Cleft Palate

Pratt¹

1985

Environmental Health Perspectives

View full text Add to dashboard Cite

Glucocorticoids (triamcinolone) and dioxins (TCDD) are highly specific teratogens in the mouse, in that cleft palate is the major malformation observed. Glucocorticoids and TCDD both readily cross the yolk sac and placenta and appear in the developing secondary palate. Structure-activity relationships for glucocorticoid-and TCDD-induced cleft palate suggest a receptor involvement. Receptors for glucocorticoids and TCDD are present in the palate and their levels in various mouse strains are highly correlated with their sensitivity to cleft palate induction. Receptors for glucocorticoids appear to be more prevalent in the palatal mesenchymal cells whereas those for TCDD are probably located in the palatal epithelial cells. Glucocorticoids exert their teratogenic effect on the palate by inhibiting the growth of the palatal mesenchymal cells whereas TCDD alters the terminal cell differentiation of the medial palatal epithelial cells. Glucocorticoid-Induced Cleft PalateGlucocorticoids administered to several species of experimental animals at midgestation inhibit complete formation of the secondary palate (1-4). Development of the mammalian secondary palate is a complex process that depends upon the presence of various hormones and growth factors (5). The palatal shelves first appear as outgrowths from the maxillary process and subsequently grow in a vertical position alongside the tongue. The shelves undergo a rapid reorientation to the horizontal position above the tongue which brings the apposing epithelia into contact at the midline. The medial epithelial cells then undergo a programmed cell death with resorption ofthe basement membrane and cell remnants, and the two shelves fuse into a single tissue, the secondary palate, which separates the oral and nasal cavities (6,7).Different strains of inbred mice exhibit different degrees of susceptibility to glucocorticoid-induced cleft palate (1,8 (5,11,12). Walker and Fraser (6) showed that during normal development, the palatal shelves became horizontal later in the A/J than the C57BL/6J strain and suggested that this difference makes A/J mice more susceptible to cortisone than C57BL/6J mice (13). A recent study utilizing frozen sections (14) showed that, in addition to delaying palatal shelf elevation, cortisone treatment severely reduced the extent of contact between the palatal shelves in A/J mice. Although contact was present in 20% of the cortisone-treated fetuses, the mean area of the shelf contact was only 20% of that in control palates. Therefore, the net shelf contact in cortisone-treated litters was only 4% of the potential contact in control litters. Other studies in which shelf contact was assessed in glucocorticoid-treated fetuses reported contact in 27-30% of the fetuses. However, this limited contact, observed between the shelves in the midpalate region, was considered adequate for complete palatal fusion, and a failure in the fusion mechanism was proposed as an alternative (4,15). Diewert and Pratt (14) also observed shelf contact in the midpalate re...

show abstract

Section: Glucocorticoid-induced Cleft Palatesupporting

confidence: 89%

Receptor-Dependent Mechanisms of Glucocorticoid and Dioxin-Induced Cleft Palate

Pratt¹

1985

Environmental Health Perspectives

View full text Add to dashboard Cite

show abstract

Developmental expression and CORT-regulation of TGF-β and EGF receptor mRNA during mouse palatal morphogenesis: Correlation between CORT-induced cleft palate and TGF-β2 mRNA expression

et al. 1996

View full text Add to dashboard Cite

Glucocorticoids (CORT) have been shown to induce cleft palate in mice. Although the pathogenetic pathway of CORT‐induced cleft palate has been investigated for several decades, the molecular details remain to be elucidated. Since growth factors have been shown to regulate palate morphogenesis, and the expression of several growth factors or their receptors, e.g. TGF‐β, EGF receptor (EGF‐R), are known to be modulated by CORT, we postulate that CORT modulation of growth factor (or receptor) gene expression is a key mechanism involved in CORT‐induced cleft palate. To test this hypothesis, we analyzed the steady‐state levels (Northern and RNase protection) and developmental expression (in situ hybridization) of four CORT‐responsive genes—TGF‐β1, TGF‐β2, TGF‐β3, and EGF receptor (EGF‐R)—in developing mouse palates in the presence or absence of exogenous CORT. Pregnant B10.A dams were injected on day 12 of gestation with CORT or sham‐injected and embryonic palates were collected at 1, 2, and 3 days postinjection (E13–E15). During mouse palate development, significant increases in TGF‐β1 and TGF‐β3 mRNA levels, as well as a significant decrease in TGF‐β2 mRNA levels, are detected; no significant difference in EGF‐R transcript level is observed with progressive development. In CORT‐exposed palates, we demonstrate no significant differences in the direction or magnitude of change with time in TGF‐β1, TGF‐β3, and EGF‐R mRNA levels compared to controls. However, CORT delays by 1 day the down‐regulation of palatal TGF‐β2 transcript normally seen on day 14 of gestation. TGF‐β2 is known to inhibit cell proliferation. The level of TGF‐β2 mRNA, the only isoform primarily expressed in the palatal mesenchyme, significantly decreases with progressive palatal development; this down‐regulation in TGF‐β2 expression is associated with increased mesenchymal cell proliferation and palatal shelf growth. CORT, at a critical stage of palatogenesis, induces a delay in the normal down‐regulation of TGF‐β2 gene expression. Given that CORT is known to inhibit mesenchymal cell proliferation and palatal shelf growth, we conclude that the CORT‐induced delay in the normal down‐regulation of TGF‐β2 gene expression is probably a key event in the pathogenesis of CORT‐induced cleft palate. © 1996 Wiley‐Liss, Inc.

show abstract

Inhibition of growth in vitro by glucocorticoids in mouse embryonic facial mesenchyme cells

Salomon

Pratt

1978

Journal Cellular Physiology

View full text Add to dashboard Cite

The growth of primary embryonic facial mesenchyme cells established from cleft palate sensitive A/J and resistant C57BL/6J (C57) mice is inhibited by glucocorticoid treatment. A reduction in cell number in both A/J and C57 culture is accompanied by a significant decrease in [3H] thymidine incorporation into both acid soluble and insoluble material. No significant changes in total cellular protein or [14C] leucine incorporation were observed in either cell type. A greater reduction in [3H] thymidine incorporation occurs in cells undergoing exponential growth following steroid exposure than in cells approaching stationary growth. In both A/J and C57 cultures the reduction in cell number exhibits a dose-dependent response to dexamethasone; is specific for glucocorticoids; and is dependent upon the concentration of serum in which the cells are maintained. A/J cells show a greater sensitivity to the inhibitory effect of dexamethasone on cell number and thymidine incorporation than comparably treated C57 cells. Specific, high affinity, saturable cytoplasmic receptors for [3H] dexamethasone are present in the maxillary cytosols from which the primary cultures were established. These receptors exhibit binding specificity for glucocorticoids, and have properties which are similar to glucocorticoid receptors identified in other systems. In both cell types, a correlation exists between the degree of growth inhibition or reduction of [3H] thymidine incorporation and the level of glucocorticoid receptors. These results provide evidence for a receptor-mediated set of responses to glucocorticoids in these cells.

show abstract

Labeling Index and Cellular Density in Palatine Shelves of Cleft-Palate Mice

Cited by 24 publications

References 7 publications

Receptor-Dependent Mechanisms of Glucocorticoid and Dioxin-Induced Cleft Palate

Receptor-Dependent Mechanisms of Glucocorticoid and Dioxin-Induced Cleft Palate

Developmental expression and CORT-regulation of TGF-β and EGF receptor mRNA during mouse palatal morphogenesis: Correlation between CORT-induced cleft palate and TGF-β2 mRNA expression

Inhibition of growth in vitro by glucocorticoids in mouse embryonic facial mesenchyme cells

Contact Info

Product

Resources

About