GSE185279
A neural crest-specific overexpression mice model reveals the transcriptional regulatory effects of Dlx2 during maxillary process development
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. Overall design: Bulk RNA sequencing of E12.5 WT and Wnt1cre; Rosa26Dlx2/-  mouse embryonic maxillary prominence tissue. Three biological replicates per group