Project description:Fibroblast growth factors (FGFs) are master regulators of organogenesis and tissue homeostasis. We generated FGF receptor (FGFR)-deficient mice to unravel their functions in the skin. These mice revealed interesting phenotypic abnormalities, including loss of skin appendages, cutaneous inflammation, keratinocyte hyperproliferation, and acanthosis. To gain insight into the underlying molecular mechanisms, we wanted to identify genes, which are differentially expressed in the skin of wild-type and mutant mice before the onset of phenotypic alterations.
Project description:Human glioblastoma cell lines L0, L1, L2 (Deleyrolle et al. Brain 2010) were transduced with lentivirus vectors expressing scrambled control (shCo), FGFR1 knockdown (shFGFR1), or FGFR2 knockdown (shFGFR2) sequences. Cells were cultured in N2 medium containing EGF and stimulated with FGF2 for 48 hours prior to RNA extraction.
Project description:Gene expression analysis revealed that the DP transcriptome is altered in the Fgfr1/Fgfr2 double mutant. At P14 the expression of 188 genes was significantly altered. At P16 the expression of 1082 genes were significantly altered.
Project description:Transcripts identified by microarray analysis that were deregulated in E14.5 Tbx18(cre/+) FGFR1(fl/fl) FGFR2(fl/fl) (Fgfr1/2cDKO) ureters
Project description:Expression of enzymatically inactive caspase-8, or deletion of caspase-8 from basal epidermal keratinocytes, triggers chronic skin inflammation in mice. Unlike similar inflammation resulting from arrest of NF-kB activation in the epidermal cells, the effect induced by caspase-8 deficiency did not depend on TNF, IL1, dermal macrophage function, or expression of the Toll-like receptor adapter proteins MyD88 or TRIF. Both interferon regulatory factor (IRF)3 and TANK-binding kinase were constitutively phosphorylated in the caspase-8-deficient epidermis, and knockdown of IRF3 in the epidermis-derived cells from these mice abolished the expression of upregulated genes. Temporal and spatial analyses of the alterations in gene expression that result from caspase-8 deficiency reveal that the changes are initiated before birth, around the time that cornification develops, and occur mainly in the suprabasal layer. Finally, we found that caspase-8-deficient keratinocytes display an enhanced response to gene activation by transfected DNA. Our findings suggest that an enhanced response to endogenous activators of IRF3 in the epidermis, presumably generated in association with keratinocyte differentiation, contributes to the skin inflammatory process triggered by caspase-8 deficiency. Total RNA was extracted from the dermis or epidermis derived from Casp-8F/–K5-Cre and Casp-8F/+K5-Cre mice at P3. RNA from two or three mice of each genotype was pooled prior to sample processing for microarray analysis. The appropriate pairs of RNA samples suited for a direct comparison of the two different genotypes under examination were differently labeled and subsequently co-hybridized onto one microarray (dual color design).
Project description:Transcripts identified by microarray analysis that were deregulated in E15.5+6d Tbx18(cre/+) FGFR1(fl/fl) FGFR2(fl/fl) (Fgfr1/2cDKO) ureter cultures