Wnt signaling pathway plays critical roles in a variety of embryonic developmental processes and also controls homeostatic selfrenewal in a number of adult tissues(Flaherty and Dawn,2008;Nusse and Clevers,2017).At the...Wnt signaling pathway plays critical roles in a variety of embryonic developmental processes and also controls homeostatic selfrenewal in a number of adult tissues(Flaherty and Dawn,2008;Nusse and Clevers,2017).At the cell membrane,Wnt ligands bind to the seven transmembrane receptors of Frizzled family and the co-receptors to activate intracellular signaling pathway,including theβ-catenin-dependent canonical Wnt signaling pathway,the noncanonical planar cell polarity(PCP)pathway and the Wnt/calcium pathway(Flaherty and Dawn,2008).In mammals,WNT4,WNT5A.展开更多
Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis;however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription...Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis;however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription repressor required for palate development. Here, we investigate the role of Msx1 in regional patterning of the secondary palate. The Wnt1-Cre-mediated expression of Msx1(Rosa Msx1^(Wnt1-Cre))throughout the palatal mesenchyme leads to cleft palate in mice, associated with aberrant cell proliferation and cell death. Osteogenic patterning of the hard palate in Rosa Msx1^(Wnt1-Cre)mice is severely impaired, as revealed by a marked reduction in palatine bone formation and decreased expression of the osteogenic regulator Sp7. Overexpression and knockout of Msx1 in mice show that the transcription repressor promotes the expression of the anterior palate-specific Alx1 but represses the expression of the medialposterior palate genes Barx1, Meox2, and Tbx22. Furthermore, Tbx22 constitutes a direct Msx1 target gene in the secondary palate, suggesting that Msx1 can directly repress the expression of medial-posterior specific genes. Finally, we determine that Sp7 is downstream of Tbx22 in palatal mesenchymal cells,suggesting that a Msx1/Tbx22/Sp7 axis participates in the regulation of palate development. Our findings unveil a novel role for Msx1 in regulating the anterior-posterior growth and patterning of the secondary palate.展开更多
Dear Editor,Although various components of the Wnt/β-catenin pathway have been investigated,there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation.For instanc...Dear Editor,Although various components of the Wnt/β-catenin pathway have been investigated,there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation.For instance,theΔExon3 mutation ofβ-catenin[1-4],which stabilizesβ-catenin by deletion of the phosphorylation site for the destruction complex,signifi cantly inhibits the differentiation of oligodendrocytes,展开更多
基金supported by grants from the National Natural Science Foundation of China(81771028)the Natural Scientific Foundation of Zhejiang Province(LY16C120002)the Key medical disciplines of Hangzhou。
文摘Wnt signaling pathway plays critical roles in a variety of embryonic developmental processes and also controls homeostatic selfrenewal in a number of adult tissues(Flaherty and Dawn,2008;Nusse and Clevers,2017).At the cell membrane,Wnt ligands bind to the seven transmembrane receptors of Frizzled family and the co-receptors to activate intracellular signaling pathway,including theβ-catenin-dependent canonical Wnt signaling pathway,the noncanonical planar cell polarity(PCP)pathway and the Wnt/calcium pathway(Flaherty and Dawn,2008).In mammals,WNT4,WNT5A.
基金supported by grants from the National Natural Scientific Foundation of China (81771028 and 317771593)Medical Health Science and Technology Project of Zhejiang (2021KY891)Medical Health Science and Technology Major Project of Hangzhou (Z20200046)。
文摘Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis;however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription repressor required for palate development. Here, we investigate the role of Msx1 in regional patterning of the secondary palate. The Wnt1-Cre-mediated expression of Msx1(Rosa Msx1^(Wnt1-Cre))throughout the palatal mesenchyme leads to cleft palate in mice, associated with aberrant cell proliferation and cell death. Osteogenic patterning of the hard palate in Rosa Msx1^(Wnt1-Cre)mice is severely impaired, as revealed by a marked reduction in palatine bone formation and decreased expression of the osteogenic regulator Sp7. Overexpression and knockout of Msx1 in mice show that the transcription repressor promotes the expression of the anterior palate-specific Alx1 but represses the expression of the medialposterior palate genes Barx1, Meox2, and Tbx22. Furthermore, Tbx22 constitutes a direct Msx1 target gene in the secondary palate, suggesting that Msx1 can directly repress the expression of medial-posterior specific genes. Finally, we determine that Sp7 is downstream of Tbx22 in palatal mesenchymal cells,suggesting that a Msx1/Tbx22/Sp7 axis participates in the regulation of palate development. Our findings unveil a novel role for Msx1 in regulating the anterior-posterior growth and patterning of the secondary palate.
基金supported by the National Basic Research Development Program of China (2013CB531303, 2012CB910402)the National Natural Science Foundation of China (31101642, 31372150)+1 种基金the Science and Technology Key Project of Zhejiang Province, China (2011C13030)the National Institutes of Health, USA (R01-NS37717)
文摘Dear Editor,Although various components of the Wnt/β-catenin pathway have been investigated,there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation.For instance,theΔExon3 mutation ofβ-catenin[1-4],which stabilizesβ-catenin by deletion of the phosphorylation site for the destruction complex,signifi cantly inhibits the differentiation of oligodendrocytes,
