Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse. The objective of this study was to search for new genes involved in mouse palate formation. Gene expression of murine embryonic palatal tissue was analyzed at the various developmental stages before, during, and after palate fusion using GeneChip? microarrays. Ceacam1 was one of the highly up-regulated genes during and after fusion in palate formation, and this was confirmed by quantitative real-time PCR. Immunohistochemical staining showed that CEACAM1 was expressed at a very low level in palatal epithelium before fusion, but highly expressed in the midline of the palate during and after fusion. To investigate the developmental role of CEACAM1, function-blocking antibody was added to embryonic mouse palate in organ culture. Palatal fusion was inhibited by this function-blocking antibody. To investigate the subsequent developmental role of CEACAM1, we characterized Ceacam1-deficient (Ceacam1-/-) mice. Epithelial cells persisted abnormally at the midline of the embryonic palate even on day E16.0, and palatal fusion was delayed in Ceacam1-/- mice. TGF?3 expression, apoptosis, and cell proliferation in palatal epithelium were not effected in the palate of Ceacam1-/-mice. CEACAM1 expression was down-regulated in Tgfb3-/- palate. However, exogenous TGF?3 did not induce CEACAM1 expression. These results suggest that CEACAM1 has roles in both the initiation of palate formation via epithelial cell adhesion and TGF signaling has some indirect effect on CEACAM1.
Regulation of the epithelial adhesion molecule CEACAM1 is important for palate formation.
Sex, Specimen part
View SamplesThe significant changes of hematopoietic cells induced by Xbp1S expression indicate that there is global alteration in gene expression. UPR induces transcription of Xbp1, and phosphorylation of the ER transmembrane kinase IRE1 initiates UPR-mediated mRNA splicing of Xbp1, resulting in the production of Xbp1S, an active form of a basic leucine zipper transcription factor. In the present study, Xbp1S retrovirus vector infected 32cl3 cells show cell cycle arrest and myeloid differentiation. Xbp1S may modulate important genes of differentiation and the cell cycle.
No associated publication
Specimen part
View SamplesEfferent inhibition of cochlear outer hair cells is mediated by nicotinic cholinergic receptors containing alpha9 (a9) and alpha10 subunits. Mice lacking a9 nicotinic subunits fail to exhibit classic olivocochlear responses and are characterized by abnormal synaptic morphology at the base of outer hair cells. To detail molecular changes induced upon the loss of a9 subunit, we sampled cochlear RNA from wild type and a9 null mice at postnatal (P) days spanning periods of synapse formation and maturation (P3, P7, P13 and P60). Our findings point to a delay in cochlear maturation starting at the onset of hearing (P13), as well as an up-regulation of various GABA receptor subunits in adult mice lacking the a9 nicotinic subunit.
Lack of nAChR activity depresses cochlear maturation and up-regulates GABA system components: temporal profiling of gene expression in alpha9 null mice.
Specimen part
View SamplesExpression profiles in mouse liver exposed to long-term gamma-irradiation were examined to assess in vivo effects of low dose-rate radiation. Three groups of male C57BL/6J mice were exposed to whole body irradiation at dose-rates of 17-20 mGy/day, 0.86-1.0 mGy/day or 0.042-0.050 mGy/day for 401-485 days (cumulative doses were approximately 8 Gy, 0.4 Gy or 0.02 Gy, respectively).
Gene expression profiles in mouse liver after long-term low-dose-rate irradiation with gamma rays.
Sex, Specimen part
View SamplesThe aim of this study was to investigate the inhibitory effect of TSU68, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFR) and fibroblast growth factor receptor 1 (FGFR1), on colon cancer liver metastasis and to test the hypothesis that TSU68 modulates the microenvironment in the liver before the formation of metastasis.
TSU68 prevents liver metastasis of colon cancer xenografts by modulating the premetastatic niche.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View Samplesgene expression data from wild-type and Bcl6-/- regulatory T cells
Bcl6 controls the Th2 inflammatory activity of regulatory T cells by repressing Gata3 function.
Specimen part
View SamplesGene expression data from wild-type and Bcl6-/- naive CD4 T cells
No associated publication
Specimen part
View SamplesGene expression data from wild-type and Bcl6-/- naive CD4 T cells
No associated publication
Specimen part
View SamplesThe NF-B pathway is a critical regulator of the immune system and has been implicated in cellular transformation and tumorigenesis. NF-B response is regulated by the activation state of the IB kinase (IKK) complex and triggered by a wide spectrum of stimuli. We previously reported that NF-B is downstream of Notch1 in T cell acute lymphoblastic leukaemia (T-ALL), however both the mechanisms involving Notch1-induced NF-B activation and the potential importance of NF-B in the maintenance of the disease are unknown. Here we visualize Notch-induced NF-B activation using both human T-ALL cell lines and animal models of this type of leukemia. We show that it is not Notch1 itself but Hes1, a canonical Notch target, the responsible for sustaining IKK activation in T-ALL. Hes1 exerts its effects by a direct transcriptional repression of the deubiquitinating enzyme CYLD, a well-characterized IKK inhibitor. Consistently, CYLD expression is significantly reduced in primary T-ALL leukemias. Finally, we demonstrate that IKK complex inhibition is a promising option for the targeted therapy of T-ALL as suppression of IKK function affected both the survival of human T-ALL cells in vitro and the maintenance of the disease in vivo.
The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia.
Specimen part, Cell line
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