摘要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(RosaMsx 1Wnt1-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 RosaMsx1Wnt1-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 pro-motes the expression of the anterior palate-specific Alx1 but represses the expression of the medial-posterior 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.