Project description:Transcription factor Dlx2 plays an important role in craniomaxillofacial development. Overexpression or null mutation can lead to craniomaxillofacial malformation in mice. Although some in vivo or in vitro experiments have explored part information about the mechanism of Dlx2 regulation, there is still a lack of complete description. Using a mouse model that can stably overexpress Dlx2 in neural crest cells, the authors conducted bulk RNA-Seq, scRNA-Seq and CUT&Tag on the early maxillary processes of mice, and comprehensively described the effects of Dlx2 overexpression on the early development of maxillary processes. Bulk RNA-Seq results showed that Dlx2 had greater interference on nerve development at E10.5, and gradually affected bone development at E12.5. ScRNA-Seq proved that overexpression of Dlx2 did not change the differentiation type of mesenchymal cells during this development process, but it would restrict the proliferation of cells and make mesenchymal cells differentiate prematurely, thus limiting the development of maxillary. CUT&Tag suggested that this regulatory process is closely related to Notch signaling pathway, and MNT and RUNX2, as direct downstream regulatory target genes of Dlx2, also play a very critical role.
Project description:Transcription factor Dlx2 plays an important role in craniomaxillofacial development. Overexpression or null mutation can lead to craniomaxillofacial malformation in mice. Although some in vivo or in vitro experiments have explored part information about the mechanism of Dlx2 regulation, there is still a lack of complete description. Using a mouse model that can stably overexpress Dlx2 in neural crest cells, the authors conducted bulk RNA-Seq, scRNA-Seq and CUT&Tag on the early maxillary processes of mice, and comprehensively described the effects of Dlx2 overexpression on the early development of maxillary processes. Bulk RNA-Seq results showed that Dlx2 had greater interference on nerve development at E10.5, and gradually affected bone development at E12.5. ScRNA-Seq proved that overexpression of Dlx2 did not change the differentiation type of mesenchymal cells during this development process, but it would restrict the proliferation of cells and make mesenchymal cells differentiate prematurely, thus limiting the development of maxillary. CUT&Tag suggested that this regulatory process is closely related to Notch signaling pathway, and MNT and RUNX2, as direct downstream regulatory target genes of Dlx2, also play a very critical role.
Project description:Transcription factor Dlx2 plays an important role in craniomaxillofacial development. Overexpression or null mutation can lead to craniomaxillofacial malformation in mice. Although some in vivo or in vitro experiments have explored part information about the mechanism of Dlx2 regulation, there is still a lack of complete description. Using a mouse model that can stably overexpress Dlx2 in neural crest cells, the authors conducted bulk RNA-Seq, scRNA-Seq and CUT&Tag on the early maxillary processes of mice, and comprehensively described the effects of Dlx2 overexpression on the early development of maxillary processes. Bulk RNA-Seq results showed that Dlx2 had greater interference on nerve development at E10.5, and gradually affected bone development at E12.5. ScRNA-Seq proved that overexpression of Dlx2 did not change the differentiation type of mesenchymal cells during this development process, but it would restrict the proliferation of cells and make mesenchymal cells differentiate prematurely, thus limiting the development of maxillary. CUT&Tag suggested that this regulatory process is closely related to Notch signaling pathway, and MNT and RUNX2, as direct downstream regulatory target genes of Dlx2, also play a very critical role.
Project description:Transcription factor Dlx2 plays an important role in craniomaxillofacial development. Overexpression or null mutation can lead to craniomaxillofacial malformation in mice. Although some in vivo or in vitro experiments have explored part information about the mechanism of Dlx2 regulation, there is still a lack of complete description. Using a mouse model that can stably overexpress Dlx2 in neural crest cells, the authors conducted bulk RNA-Seq, scRNA-Seq and CUT&Tag on the early maxillary processes of mice, and comprehensively described the effects of Dlx2 overexpression on the early development of maxillary processes. Bulk RNA-Seq results showed that Dlx2 had greater interference on nerve development at E10.5, and gradually affected bone development at E12.5. ScRNA-Seq proved that overexpression of Dlx2 did not change the differentiation type of mesenchymal cells during this development process, but it would restrict the proliferation of cells and make mesenchymal cells differentiate prematurely, thus limiting the development of maxillary. CUT&Tag suggested that this regulatory process is closely related to Notch signaling pathway, and MNT and RUNX2, as direct downstream regulatory target genes of Dlx2, also play a very critical role.
Project description:Craniofacial morphogenesis is an intricate process that requires precise regulation of cell proliferation, migration, and differentiation. Perturbations of this process cause a series of craniofacial deformities. Dlx2 is a critical transcription factor that regulates the development of the first branchial arch. However, the transcriptional regulatory functions of Dlx2 during craniofacial development have been poorly understood due to the lack of animal models in that the levels of Dlx2 can be precisely modulated. In this study, we constructed a Rosa26 site-directed Dlx2 gene knock-in mouse model Rosa26CAG-LSL-Dlx2-3xFlag for conditionally overexpressing Dlx2. By breeding with Wnt1cre mice, we obtained Wnt1cre; Rosa26Dlx2/- mice in which Dlx2 is overexpressed in neural crest lineage at about three times the endogenous level. The Wnt1cre; Rosa26Dlx2/- mice exhibited consistent phenotypes that include cleft palate across generations and individual animals. Using this model, we demonstrated that Dlx2 caused cleft palate by affecting maxillary growth in the early-stage development of maxillary prominences. By performing bulk RNA-seq, we demonstrated that the overexpression of Dlx2 induced significant changes of many genes related to critical developmental pathways. In summary, our novel mouse model provides a reliable and consistent system for investigating the functions of Dlx2 during development and for dissecting the gene regulatory networks underlying craniofacial development.
Project description:A neural crest-specific overexpression mice model reveals the transcriptional regulatory effects of Dlx2 during maxillary process development