The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Yang Chai - One of the best experts on this subject based on the ideXlab platform.
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tgfβ regulates epithelial mesenchymal interactions through wnt signaling activity to control muscle development in the soft Palate
Development, 2014Co-Authors: Junichi Iwata, Akiko Suzuki, Toshiaki Yokota, Richard Pelikan, Mark M Urata, Pedro A Sanchezlara, Yang ChaiAbstract:Clefting of the soft Palate occurs as a congenital defect in humans and adversely affects the physiological function of the Palate. However, the molecular and cellular mechanism of clefting of the soft Palate remains unclear because few animal models exhibit an isolated cleft in the soft Palate. Using three-dimensional microCT images and histological reconstruction, we found that loss of TGFβ signaling in the palatal epithelium led to soft Palate muscle defects in Tgfbr2fl/fl;K14-Cre mice. Specifically, muscle mass was decreased in the soft Palates of Tgfbr2 mutant mice, following defects in cell proliferation and differentiation. Gene expression of Dickkopf (Dkk1 and Dkk4), negative regulators of WNT-β-catenin signaling, is upregulated in the soft Palate of Tgfbr2fl/fl;K14-Cre mice, and WNT-β-catenin signaling is disrupted in the palatal mesenchyme. Importantly, blocking the function of DKK1 and DKK4 rescued the cell proliferation and differentiation defects in the soft Palate of Tgfbr2fl/fl;K14-Cre mice. Thus, our findings indicate that loss of TGFβ signaling in epithelial cells compromises activation of WNT signaling and proper muscle development in the soft Palate through tissue-tissue interactions, resulting in a cleft soft Palate. This information has important implications for prevention and non-surgical correction of cleft soft Palate.
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ctgf mediates smad dependent transforming growth factor β signaling to regulate mesenchymal cell proliferation during Palate development
Molecular and Cellular Biology, 2013Co-Authors: Carolina Parada, Junichi Iwata, Akiko Suzuki, Jingyuan Li, Yang ChaiAbstract:: Transforming growth factor β (TGF-β) signaling plays crucial functions in the regulation of craniofacial development, including palatogenesis. Here, we have identified connective tissue growth factor (Ctgf) as a downstream target of the TGF-β signaling pathway in palatogenesis. The pattern of Ctgf expression in wild-type embryos suggests that it may be involved in key processes during Palate development. We found that Ctgf expression is downregulated in both Wnt1-Cre; Tgfbr2(fl/fl) and Osr2-Cre; Smad4(fl/fl) Palates. In Tgfbr2 mutant embryos, downregulation of Ctgf expression is associated with p38 mitogen-activated protein kinase (MAPK) overactivation, whereas loss of function of Smad4 itself leads to downregulation of Ctgf expression. We also found that CTGF regulates its own expression via TGF-β signaling. Osr2-Cre; Smad4(fl/fl) mice exhibit a defect in cell proliferation similar to that of Tgfbr2 mutant mice, as well as cleft Palate. We detected no alteration in bone morphogenetic protein (BMP) downstream targets in Smad4 mutant Palates, suggesting that the reduction in cell proliferation is due to defective transduction of TGF-β signaling via decreased Ctgf expression. Significantly, an exogenous source of CTGF was able to rescue the cell proliferation defect in both Tgfbr2 and Smad4 mutant Palates. Collectively, our data suggest that CTGF regulates proliferation as a mediator of the canonical pathway of TGF-β signaling during palatogenesis.
Junichi Iwata - One of the best experts on this subject based on the ideXlab platform.
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tgfβ regulates epithelial mesenchymal interactions through wnt signaling activity to control muscle development in the soft Palate
Development, 2014Co-Authors: Junichi Iwata, Akiko Suzuki, Toshiaki Yokota, Richard Pelikan, Mark M Urata, Pedro A Sanchezlara, Yang ChaiAbstract:Clefting of the soft Palate occurs as a congenital defect in humans and adversely affects the physiological function of the Palate. However, the molecular and cellular mechanism of clefting of the soft Palate remains unclear because few animal models exhibit an isolated cleft in the soft Palate. Using three-dimensional microCT images and histological reconstruction, we found that loss of TGFβ signaling in the palatal epithelium led to soft Palate muscle defects in Tgfbr2fl/fl;K14-Cre mice. Specifically, muscle mass was decreased in the soft Palates of Tgfbr2 mutant mice, following defects in cell proliferation and differentiation. Gene expression of Dickkopf (Dkk1 and Dkk4), negative regulators of WNT-β-catenin signaling, is upregulated in the soft Palate of Tgfbr2fl/fl;K14-Cre mice, and WNT-β-catenin signaling is disrupted in the palatal mesenchyme. Importantly, blocking the function of DKK1 and DKK4 rescued the cell proliferation and differentiation defects in the soft Palate of Tgfbr2fl/fl;K14-Cre mice. Thus, our findings indicate that loss of TGFβ signaling in epithelial cells compromises activation of WNT signaling and proper muscle development in the soft Palate through tissue-tissue interactions, resulting in a cleft soft Palate. This information has important implications for prevention and non-surgical correction of cleft soft Palate.
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ctgf mediates smad dependent transforming growth factor β signaling to regulate mesenchymal cell proliferation during Palate development
Molecular and Cellular Biology, 2013Co-Authors: Carolina Parada, Junichi Iwata, Akiko Suzuki, Jingyuan Li, Yang ChaiAbstract:: Transforming growth factor β (TGF-β) signaling plays crucial functions in the regulation of craniofacial development, including palatogenesis. Here, we have identified connective tissue growth factor (Ctgf) as a downstream target of the TGF-β signaling pathway in palatogenesis. The pattern of Ctgf expression in wild-type embryos suggests that it may be involved in key processes during Palate development. We found that Ctgf expression is downregulated in both Wnt1-Cre; Tgfbr2(fl/fl) and Osr2-Cre; Smad4(fl/fl) Palates. In Tgfbr2 mutant embryos, downregulation of Ctgf expression is associated with p38 mitogen-activated protein kinase (MAPK) overactivation, whereas loss of function of Smad4 itself leads to downregulation of Ctgf expression. We also found that CTGF regulates its own expression via TGF-β signaling. Osr2-Cre; Smad4(fl/fl) mice exhibit a defect in cell proliferation similar to that of Tgfbr2 mutant mice, as well as cleft Palate. We detected no alteration in bone morphogenetic protein (BMP) downstream targets in Smad4 mutant Palates, suggesting that the reduction in cell proliferation is due to defective transduction of TGF-β signaling via decreased Ctgf expression. Significantly, an exogenous source of CTGF was able to rescue the cell proliferation defect in both Tgfbr2 and Smad4 mutant Palates. Collectively, our data suggest that CTGF regulates proliferation as a mediator of the canonical pathway of TGF-β signaling during palatogenesis.
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fibroblast growth factor 9 fgf9 pituitary homeobox 2 pitx2 pathway mediates transforming growth factor β tgfβ signaling to regulate cell proliferation in palatal mesenchyme during mouse palatogenesis
Journal of Biological Chemistry, 2012Co-Authors: Junichi Iwata, Carolina Parada, Akiko Suzuki, Richard Pelikan, Mark M Urata, Lily Tung, Joseph G Hacia, Liza Ramenzoni, Obaid Chaudhry, Pedro A SanchezlaraAbstract:Cleft Palate represents one of the most common congenital birth defects. Transforming growth factor β (TGFβ) signaling plays crucial functions in regulating craniofacial development, and loss of TGFβ receptor type II in cranial neural crest cells leads to craniofacial malformations, including cleft Palate in mice (Tgfbr2(fl/fl);Wnt1-Cre mice). Here we have identified candidate target genes of TGFβ signaling during palatal formation. These target genes were selected based on combining results from gene expression profiles of embryonic day 14.5 Palates from Tgfbr2(fl/fl);Wnt1-Cre mice and previously identified cleft Palate phenotypes in genetically engineered mouse models. We found that fibroblast growth factor 9 (Fgf9) and transcription factor pituitary homeobox 2 (Pitx2) expressions are significantly down-regulated in the Palate of Tgfbr2(fl/fl);Wnt1-Cre mice, and Fgf9 and Pitx2 loss of function mutations result in cleft Palate in mice. Pitx2 expression is down-regulated by siRNA knockdown of Fgf9, suggesting that Fgf9 is upstream of Pitx2. We detected decreased expression of both cyclins D1 and D3 in the Palates of Tgfbr2(fl/fl);Wnt1-Cre mice, consistent with the defect in cell proliferation. Significantly, exogenous FGF9 restores expression of cyclins D1 and D3 in a Pitx2-dependent manner and rescues the cell proliferation defect in the palatal mesenchyme of Tgfbr2(fl/fl);Wnt1-Cre mice. Our study indicates that a TGFβ-FGF9-PITX2 signaling cascade regulates cranial neural crest cell proliferation during Palate formation.
Pedro A Sanchezlara - One of the best experts on this subject based on the ideXlab platform.
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tgfβ regulates epithelial mesenchymal interactions through wnt signaling activity to control muscle development in the soft Palate
Development, 2014Co-Authors: Junichi Iwata, Akiko Suzuki, Toshiaki Yokota, Richard Pelikan, Mark M Urata, Pedro A Sanchezlara, Yang ChaiAbstract:Clefting of the soft Palate occurs as a congenital defect in humans and adversely affects the physiological function of the Palate. However, the molecular and cellular mechanism of clefting of the soft Palate remains unclear because few animal models exhibit an isolated cleft in the soft Palate. Using three-dimensional microCT images and histological reconstruction, we found that loss of TGFβ signaling in the palatal epithelium led to soft Palate muscle defects in Tgfbr2fl/fl;K14-Cre mice. Specifically, muscle mass was decreased in the soft Palates of Tgfbr2 mutant mice, following defects in cell proliferation and differentiation. Gene expression of Dickkopf (Dkk1 and Dkk4), negative regulators of WNT-β-catenin signaling, is upregulated in the soft Palate of Tgfbr2fl/fl;K14-Cre mice, and WNT-β-catenin signaling is disrupted in the palatal mesenchyme. Importantly, blocking the function of DKK1 and DKK4 rescued the cell proliferation and differentiation defects in the soft Palate of Tgfbr2fl/fl;K14-Cre mice. Thus, our findings indicate that loss of TGFβ signaling in epithelial cells compromises activation of WNT signaling and proper muscle development in the soft Palate through tissue-tissue interactions, resulting in a cleft soft Palate. This information has important implications for prevention and non-surgical correction of cleft soft Palate.
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fibroblast growth factor 9 fgf9 pituitary homeobox 2 pitx2 pathway mediates transforming growth factor β tgfβ signaling to regulate cell proliferation in palatal mesenchyme during mouse palatogenesis
Journal of Biological Chemistry, 2012Co-Authors: Junichi Iwata, Carolina Parada, Akiko Suzuki, Richard Pelikan, Mark M Urata, Lily Tung, Joseph G Hacia, Liza Ramenzoni, Obaid Chaudhry, Pedro A SanchezlaraAbstract:Cleft Palate represents one of the most common congenital birth defects. Transforming growth factor β (TGFβ) signaling plays crucial functions in regulating craniofacial development, and loss of TGFβ receptor type II in cranial neural crest cells leads to craniofacial malformations, including cleft Palate in mice (Tgfbr2(fl/fl);Wnt1-Cre mice). Here we have identified candidate target genes of TGFβ signaling during palatal formation. These target genes were selected based on combining results from gene expression profiles of embryonic day 14.5 Palates from Tgfbr2(fl/fl);Wnt1-Cre mice and previously identified cleft Palate phenotypes in genetically engineered mouse models. We found that fibroblast growth factor 9 (Fgf9) and transcription factor pituitary homeobox 2 (Pitx2) expressions are significantly down-regulated in the Palate of Tgfbr2(fl/fl);Wnt1-Cre mice, and Fgf9 and Pitx2 loss of function mutations result in cleft Palate in mice. Pitx2 expression is down-regulated by siRNA knockdown of Fgf9, suggesting that Fgf9 is upstream of Pitx2. We detected decreased expression of both cyclins D1 and D3 in the Palates of Tgfbr2(fl/fl);Wnt1-Cre mice, consistent with the defect in cell proliferation. Significantly, exogenous FGF9 restores expression of cyclins D1 and D3 in a Pitx2-dependent manner and rescues the cell proliferation defect in the palatal mesenchyme of Tgfbr2(fl/fl);Wnt1-Cre mice. Our study indicates that a TGFβ-FGF9-PITX2 signaling cascade regulates cranial neural crest cell proliferation during Palate formation.
David Beighton - One of the best experts on this subject based on the ideXlab platform.
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dental caries oral hygiene and oral clearance in children with craniofacial disorders
Journal of Dental Research, 2004Co-Authors: M Ahluwalia, Susan Brailsford, Edward Tarelli, K Barnard, S C Gilbert, D T Clark, David BeightonAbstract:The reason that children with cleft Palates tend to have a greater prevalence of tooth decay than normal children is unclear. We hypothesized that children with cleft Palates would have increased oral clearance times for foods and, consequently, higher levels of caries and caries-associated micro-organisms than control children. Children aged 6–16 yrs, with (n = 81) or without (n = 61) cleft Palates, were studied. Children with cleft Palates had DMFT and dmft scores greater (p < 0.01) than those of the control group. The number of caries-associated organisms was greater in the saliva of the cleft Palate children (all p < 0.001). The oral hygiene, plaque and gingival index scores were greater (p < 0.0001), oral clearance was longer (p < 0.01), and levels of sucrose and starch-derived saccharides higher (p < 0.01) in the cleft Palate group. However, salivary concentrations of organic acids were lower in the children with craniofacial disorders, probably reflecting the altered physiology of the more mature d...
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dental caries oral hygiene and oral clearance in children with craniofacial disorders
Journal of Dental Research, 2004Co-Authors: M Ahluwalia, Susan Brailsford, Edward Tarelli, K Barnard, S C Gilbert, D T Clark, David BeightonAbstract:The reason that children with cleft Palates tend to have a greater prevalence of tooth decay than normal children is unclear. We hypothesized that children with cleft Palates would have increased oral clearance times for foods and, consequently, higher levels of caries and caries-associated micro-organisms than control children. Children aged 6-16 yrs, with (n = 81) or without (n = 61) cleft Palates, were studied. Children with cleft Palates had DMFT and dmft scores greater (p < 0.01) than those of the control group. The number of caries-associated organisms was greater in the saliva of the cleft Palate children (all p < 0.001). The oral hygiene, plaque and gingival index scores were greater (p < 0.0001), oral clearance was longer (p < 0.01), and levels of sucrose and starch-derived saccharides higher (p < 0.01) in the cleft Palate group. However, salivary concentrations of organic acids were lower in the children with craniofacial disorders, probably reflecting the altered physiology of the more mature dental biofilm. The longer oral clearance times of foods and the consequent generation of fermentable sugars from starches may contribute to the higher caries prevalence observed in children with cleft Palates.
Akiko Suzuki - One of the best experts on this subject based on the ideXlab platform.
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tgfβ regulates epithelial mesenchymal interactions through wnt signaling activity to control muscle development in the soft Palate
Development, 2014Co-Authors: Junichi Iwata, Akiko Suzuki, Toshiaki Yokota, Richard Pelikan, Mark M Urata, Pedro A Sanchezlara, Yang ChaiAbstract:Clefting of the soft Palate occurs as a congenital defect in humans and adversely affects the physiological function of the Palate. However, the molecular and cellular mechanism of clefting of the soft Palate remains unclear because few animal models exhibit an isolated cleft in the soft Palate. Using three-dimensional microCT images and histological reconstruction, we found that loss of TGFβ signaling in the palatal epithelium led to soft Palate muscle defects in Tgfbr2fl/fl;K14-Cre mice. Specifically, muscle mass was decreased in the soft Palates of Tgfbr2 mutant mice, following defects in cell proliferation and differentiation. Gene expression of Dickkopf (Dkk1 and Dkk4), negative regulators of WNT-β-catenin signaling, is upregulated in the soft Palate of Tgfbr2fl/fl;K14-Cre mice, and WNT-β-catenin signaling is disrupted in the palatal mesenchyme. Importantly, blocking the function of DKK1 and DKK4 rescued the cell proliferation and differentiation defects in the soft Palate of Tgfbr2fl/fl;K14-Cre mice. Thus, our findings indicate that loss of TGFβ signaling in epithelial cells compromises activation of WNT signaling and proper muscle development in the soft Palate through tissue-tissue interactions, resulting in a cleft soft Palate. This information has important implications for prevention and non-surgical correction of cleft soft Palate.
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ctgf mediates smad dependent transforming growth factor β signaling to regulate mesenchymal cell proliferation during Palate development
Molecular and Cellular Biology, 2013Co-Authors: Carolina Parada, Junichi Iwata, Akiko Suzuki, Jingyuan Li, Yang ChaiAbstract:: Transforming growth factor β (TGF-β) signaling plays crucial functions in the regulation of craniofacial development, including palatogenesis. Here, we have identified connective tissue growth factor (Ctgf) as a downstream target of the TGF-β signaling pathway in palatogenesis. The pattern of Ctgf expression in wild-type embryos suggests that it may be involved in key processes during Palate development. We found that Ctgf expression is downregulated in both Wnt1-Cre; Tgfbr2(fl/fl) and Osr2-Cre; Smad4(fl/fl) Palates. In Tgfbr2 mutant embryos, downregulation of Ctgf expression is associated with p38 mitogen-activated protein kinase (MAPK) overactivation, whereas loss of function of Smad4 itself leads to downregulation of Ctgf expression. We also found that CTGF regulates its own expression via TGF-β signaling. Osr2-Cre; Smad4(fl/fl) mice exhibit a defect in cell proliferation similar to that of Tgfbr2 mutant mice, as well as cleft Palate. We detected no alteration in bone morphogenetic protein (BMP) downstream targets in Smad4 mutant Palates, suggesting that the reduction in cell proliferation is due to defective transduction of TGF-β signaling via decreased Ctgf expression. Significantly, an exogenous source of CTGF was able to rescue the cell proliferation defect in both Tgfbr2 and Smad4 mutant Palates. Collectively, our data suggest that CTGF regulates proliferation as a mediator of the canonical pathway of TGF-β signaling during palatogenesis.
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fibroblast growth factor 9 fgf9 pituitary homeobox 2 pitx2 pathway mediates transforming growth factor β tgfβ signaling to regulate cell proliferation in palatal mesenchyme during mouse palatogenesis
Journal of Biological Chemistry, 2012Co-Authors: Junichi Iwata, Carolina Parada, Akiko Suzuki, Richard Pelikan, Mark M Urata, Lily Tung, Joseph G Hacia, Liza Ramenzoni, Obaid Chaudhry, Pedro A SanchezlaraAbstract:Cleft Palate represents one of the most common congenital birth defects. Transforming growth factor β (TGFβ) signaling plays crucial functions in regulating craniofacial development, and loss of TGFβ receptor type II in cranial neural crest cells leads to craniofacial malformations, including cleft Palate in mice (Tgfbr2(fl/fl);Wnt1-Cre mice). Here we have identified candidate target genes of TGFβ signaling during palatal formation. These target genes were selected based on combining results from gene expression profiles of embryonic day 14.5 Palates from Tgfbr2(fl/fl);Wnt1-Cre mice and previously identified cleft Palate phenotypes in genetically engineered mouse models. We found that fibroblast growth factor 9 (Fgf9) and transcription factor pituitary homeobox 2 (Pitx2) expressions are significantly down-regulated in the Palate of Tgfbr2(fl/fl);Wnt1-Cre mice, and Fgf9 and Pitx2 loss of function mutations result in cleft Palate in mice. Pitx2 expression is down-regulated by siRNA knockdown of Fgf9, suggesting that Fgf9 is upstream of Pitx2. We detected decreased expression of both cyclins D1 and D3 in the Palates of Tgfbr2(fl/fl);Wnt1-Cre mice, consistent with the defect in cell proliferation. Significantly, exogenous FGF9 restores expression of cyclins D1 and D3 in a Pitx2-dependent manner and rescues the cell proliferation defect in the palatal mesenchyme of Tgfbr2(fl/fl);Wnt1-Cre mice. Our study indicates that a TGFβ-FGF9-PITX2 signaling cascade regulates cranial neural crest cell proliferation during Palate formation.
