Project description:Cleft palate is among the most common structural birth defects in humans. Previous studies have shown that mutations in FOXF2 are associated with cleft palate in humans and mice and that Foxf2 acts in a Shh-Foxf-Fgf18-Shh molecular network controlling palatal shelf growth. In this study, we generated mice carrying 3xFLAG epitope-tagged endogenous Foxf2 protein using the CRISPR/Cas9-mediated genome editing technology and characterized genome-wide Foxf2 binding sites in the developing palatal shelves using chromatin immunoprecipitation and genome sequencing (ChIP-seq). By combined analysis of ChIP-seq and RNA-seq datasets we identified a large list of Foxf2 target genes. Further analyses demonstrate that Foxf2 directly regulate expression of several genes encoding ECM or ECM modifiers during palate development. Moreover, our ChIP-seq and RNA-seq datasets provide an excellent resource for comprehensive understanding of the molecular network controlling palate development.
Project description:The tongue is a specialized muscular organ that performs multiple essential functions including mastication, deglutition, oral sensation, oral cleansing, airway maintenance and vocalization. In this study, we show Foxf1/Foxf2 serves as key mediators of hedgehog signaling in regulating myoblast migration, differentiation, and intrinsic tongue muscle organization. We took advantage of the Foxf2FLAG mice which carries 3xFLAG epitope-tagged endogenous Foxf2 protein and characterized genome-wide Foxf2 binding sites in the developing tongues using chromatin immunoprecipitation and genome sequencing (ChIP-seq). Further analyses demonstrate that Foxf1/2 transcription factors directly control the expression of Hgf, Tgfb2, and Tgfb3, to regulate tongue myogenesis.
Project description:This genome-wide gene expression studies are aimed at deciphering whether FOXF2 transcriptional activity and specificity are compromised in FOXF2-expressing breast cancer cells (MDA-MB-231) compared with FOXF2-expressing normal breast epithelial cells (MCF10A).
Project description:To identify the genes and pathways regulated by FOXF2, we investigated potential FOXF2 gene targets by microarray analyses of primary prostate stromal cells (PrSC) in which FOXF2 was knocked down by siRNA. 190 differentially expressed genes were selected, of which 104 genes were more highly expressed in PrSC cells treated with FOXF2 siRNA and 86 were more highly expressed in PRSC cells treated with negative control siRNA.
Project description:Background: The FACEBASE consortium was established in part to create a central resource for craniofacial researchers. One purpose is to provide a molecular anatomy of craniofacial development. To this end we have used a combination of laser capture microdissection and RNA-Seq to define the gene expression programs driving development of the murine palate. Results: We focused on the E14.5 palate, soon after medial fusion of the two palatal shelves. The palate was divided into multiple compartments, including medial and lateral, as well as oral and nasal, for both the anterior and posterior domains. A total of 25 RNA-Seq datasets were generated. The results provide a comprehensive view of the region specific expression of all transcription factors, growth factors and receptors. Paracrine interactions can be inferred from flanking compartment growth factor/receptor expression patterns. The results are validated primarily through very high concordance with extensive previously published gene expression data for the developing palate. In addition selected immunostain validations were carried out. Conclusions: This report provides an RNA-Seq based atlas of gene expression patterns driving palate development at microanatomic resolution. This FACEBASE resource is designed to fuel discovery by the craniofacial research community. Laser capture microdissection and RNA-seq were used to generate gene expression profiles of different compartments of the mouse E14.5 developing palate
Project description:To identify the genes and pathways regulated by FOXF2, we investigated potential FOXF2 gene targets by microarray analyses of primary prostate stromal cells (PrSC) in which FOXF2 was knocked down by siRNA. 190 differentially expressed genes were selected, of which 104 genes were more highly expressed in PrSC cells treated with FOXF2 siRNA and 86 were more highly expressed in PRSC cells treated with negative control siRNA. Experiment Overall Design: In each experiment, we compared gene expression of PrSC cells treated with FOXF2 siRNA versus PrSC cells treated with negative control siRNA, in a total of 6 affymetrix arrays. 190 differentially expressed genes were selected (ratio negative control siRNA/siRNA ⥠2log |0.8| as average in all arrays).
Project description:Brain of the foxf2 mutant mouse embryo shows microvascular aneurysm, underdeveloped blood brain barrier and also significant defects in the tissue integrity. Foxf2 expresses in the pericytes of the brain and seem to play an important role in proper development of the BBB. Brains of E18.5 wt and foxf2 mutant mouse embryos dissected and RNA extracted from the brains using Sigma mammalian total RNA extraction kit. The RNA then been sent to th core facility for hybridization.