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Canonical Wnt Signaling Pathway (canonical + wnt_signaling_pathway)
Selected AbstractsThe canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Frank Abstract The evolutionarily conserved canonical Wnt-,-catenin-T cell factor (TCF)/lymphocyte enhancer binding factor (LEF) signaling pathway regulates key checkpoints in the development of various tissues. Therefore, it is not surprising that a large body of gain-of-function and loss-of-function studies implicate Wnt-,-catenin signaling in lymphopoiesis and hematopoiesis. In contrast, recent papers have reported that Mx-Cre-mediated conditional deletion of ,-catenin and/or its homolog ,-catenin (plakoglobin) did not impair hematopoiesis or lymphopoiesis. However, these studies also report that TCF reporter activity remains active in ,-catenin- and ,-catenin-deficient hematopoietic stem cells and all cells derived from these precursors, indicating that the canonical Wnt signaling pathway was not abrogated. Therefore, these studies in fact show that the canonical Wnt signaling pathway is important in hematopoiesis and lymphopoiesis, even though the molecular basis for the induction of the reporter activity is currently unknown. In this perspective, we provide a broad background to the field with a discussion of the available data and create a framework within which the available and future studies may be evaluated. [source] Frizzled-1 is involved in the neuroprotective effect of Wnt3a against A, oligomersJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2008Marcelo A. Chacón The activation of the canonical Wnt signaling pathway protects hippocampal neurons against the toxicity of Alzheimer's amyloid-,-peptide (A,), however, the role played by the Wnt receptors Frizzleds, has not been studied. We report here that Frizzled-1 mediates the activation of the canonical Wnt/,-catenin pathway by Wnt3a in PC12 cells. In addition, the protective effect of Wnt3a against the toxicity of A, oligomers was modulated by Frizzled-1 expression levels in both PC12 cells and hippocampal neurons. Over-expression of Frizzled-1 significantly increased cell survival induced by Wnt3a and diminished caspase-3 activation, while knocking-down Frizzled-1 expression by antisense oligonucleotides decreased the Wnt3a protection. Over-expression of wild-type ,-catenin, but not a transcriptionally inactive mutated version, prevented the toxicity of A, suggesting that the transcription of Wnt target genes may be involved in these events. This was confirmed by co-transfecting both Frizzled-1 and the inactive form of ,-catenin, which does not elicited protection levels similar to those showed with endogenous ,-catenin. Our results indicate that Wnt3a protects from A,-oligomers toxicity by activating the canonical Wnt signaling pathway through the Frizzled-1 receptor, suggesting a therapeutic potential for this signaling pathway in the treatment of Alzheimer's disease. J. Cell. Physiol. 217: 215,227, 2008. © 2008 Wiley-Liss, Inc. [source] Pulsating fluid flow modulates gene expression of proteins involved in Wnt signaling pathways in osteocytesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2009Ana Santos Abstract Strain-derived flow of interstitial fluid activates signal transduction pathways in osteocytes that regulate bone mechanical adaptation. Wnts are involved in this process, but whether mechanical loading modulates Wnt signaling in osteocytes is unclear. We assessed whether mechanical stimulation by pulsating fluid flow (PFF) leads to functional Wnt production, and whether nitric oxide (NO) is important for activation of the canonical Wnt signaling pathway in MLO-Y4 osteocytes. MC3T3-E1 osteoblasts were studied as a positive control for the MLO-Y4 osteocyte response to mechanical loading. MLO-Y4 osteocytes and MC3T3-E1 osteoblasts were submitted to 1-h PFF (0.7,±,0.3 Pa, 5 Hz), and postincubated (PI) without PFF for 0.5,3 h. Gene expression of proteins related to the Wnt canonical and noncanonical pathways were studied using real-time polymerase chain reaction (PCR). In MLO-Y4 osteocytes, PFF upregulated gene expression of Wnt3a, c-jun, connexin 43, and CD44 at 1,3-h PI. In MC3T3-E1 osteoblasts, PFF downregulated gene expression of Wnt5a and c-jun at 0.5,3-h PI. In MLO-Y4 osteocytes, gene expression of PFF-induced Wnt target genes was suppressed by the Wnt antagonist sFRP4, suggesting that loading activates the Wnt canonical pathway through functional Wnt production. The NO inhibitor L-NAME suppressed the effect of PFF on gene expression of Wnt target genes, suggesting that NO might play a role in PFF-induced Wnt production. The response to PFF differed in MC3T3-E1 osteoblasts. Because Wnt signaling is important for bone mass regulation, osteocytes might orchestrate loading-induced bone remodeling through, among others, Wnts. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1280,1287, 2009 [source] The molecular basis of oral-facial-digital syndrome, type 1,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 4 2009Marina Macca Abstract Oral,facial,digital syndrome type 1 (OFDI; OFD1; OMIM 311200) is a rare developmental disorder transmitted as an X-linked dominant condition with embryonic male lethality. OFD1 is characterized by malformation of the oral cavity, face, and digits. Central nervous system (CNS) abnormalities and cystic kidney disease can also be part of this condition. This disorder is due to mutations in the OFD1 gene that encodes a centrosomal protein localized at the basal bodies at the origin of primary cilia. Characterization of in vitro and in vivo models demonstrated that, similarly to what described for other ciliary proteins, Ofd1 inactivation is associated to defective sonic hedgehog (Shh) and canonical Wnt signaling pathways. Functional studies have demonstrated that OFD1 has a crucial role in the biology of primary cilia thus ascribing this pleiotropic disease to the growing number of disorders associated to dysfunction of primary cilia. OFD1 shares phenotypic similarities with this latter group of disorders, such as cystic kidneys, skeletal, and CNS abnormalities. Future studies will address whether all clinical manifestations of these diseases can be entirely explained by cilia dysfunction or may also be due to direct roles of the proteins involved. © 2009 Wiley-Liss, Inc. [source] | ||||||||||