Key Regulatory Molecules (key + regulatory_molecule)

Distribution by Scientific Domains

Selected Abstracts

GATA factors as key regulatory molecules in the development of Drosophila endoderm

Ryutaro Murakami
Essential roles for GATA factors in the development of endoderm have been reported in various animals. A Drosophila GATA factor gene, serpent (srp, dGATAb, ABF), is expressed in the prospective endoderm, and loss of srp activity causes transformation of the prospective endoderm into ectodermal foregut and hindgut, indicating that srp acts as a selector gene to specify the developmental fate of the endoderm. While srp is expressed in the endoderm only during early stages, it activates a subsequent GATA factor gene, dGATAe, and the latter continues to be expressed specifically in the endoderm throughout life. dGATAe activates various functional genes in the differentiated endodermal midgut. An analogous mode of regulation has been reported in Caenorhabditis elegans, in which a pair of GATA genes, end-1/3, specifies endodermal fate, and a downstream pair of GATA genes, elt-2/7, activates genes in the differentiated endoderm. Functional homology of GATA genes in nature is apparently extendable to vertebrates, because endodermal GATA genes of C. elegans and Drosophila induce endoderm development in Xenopus ectoderm. These findings strongly imply evolutionary conservation of the roles of GATA factors in the endoderm across the protostomes and the deuterostomes. [source]

Genetic redundancy in human cervical carcinoma cells: Identification of cells with "normal" properties

Anastasia Bachmann
Abstract Although it is generally assumed that cancer arises from a singular cell, a tumor must be considered as a dynamic and emergent biological structure, whose organizing principle is determined by genetic and epigenetic modifications, occurring variably in response to microenvironmental selection conditions. As previously shown, HPV-positive cervical carcinoma cells have lost their ability to induce IFN-, upon TNF-, treatment. However, regarding cancer as a non-linear system, which may, even in the absence of an apparent selection pressure, fluctuate between different "metastable" phenotypes, we demonstrate that TNF-, mediated IFN-, induction is not irreversibly disturbed in all cells. Using the IFN-, sensitive Encephalomyocarditis virus (EMCV) as a tool to monitor antiviral activity in long-term established malignant HeLa cells, rare IFN-, expressing clones were rescued from a population of non-responsive and EMCV-sensitive cells. Antiviral activity was mediated by the re-expression of IRF-1 and p48 (IRF-9), both key regulatory molecules normally found to be suppressed in cervical carcinoma cells. Upon inoculating of selected clones into immunocompromised animals, a reduced or even an absence of tumorigenicity of initially highly malignant cells could be discerned. These data indicate that both the absence of interferon signaling and the ability to form tumors were reversed in a minority of cells. We provide a paradigm for the existence of innate genetic redundancy mechanisms, where a particular phenotype persists and can be isolated without application of drugs generally changing the epigenetic context. 2007 Wiley-Liss, Inc. [source]

Normal and abnormal development of the urogenital tract

Peter M. Cuckow
Abstract An understanding of the normal development of the urogenital tract, at both the structural and molecular level, gives an insight into the mechanisms involved in renal pathology. In this review we will outline embryology of normal and abnormal renal development and discuss the function of some of the key regulatory molecules which have been described recently. Copyright 2001 John Wiley & Sons, Ltd. [source]

Fibroblast growth factor 2 is an intrinsic chondroprotective agent that suppresses ADAMTS-5 and delays cartilage degradation in murine osteoarthritis

Shi-Lu Chia
Objective We have previously identified in articular cartilage an abundant pool of the heparin-binding growth factor, fibroblast growth factor 2 (FGF-2), which is bound to the pericellular matrix heparan sulfate proteoglycan, perlecan. This pool of FGF-2 activates chondrocytes upon tissue loading and is released following mechanical injury. In vitro, FGF-2 suppresses interleukin-1,driven aggrecanase activity in human cartilage explants, suggesting a chondroprotective role in vivo. We undertook this study to investigate the in vivo role of FGF-2 in murine cartilage. Methods Basal characteristics of the articular cartilage of Fgf2,/, and Fgf2+/+ mice were determined by histomorphometry, nanoindentation, and quantitative reverse transcriptase,polymerase chain reaction. The articular cartilage was graded histologically in aged mice as well as in mice in which osteoarthritis (OA) had been induced by surgical destabilization of the medial meniscus. RNA was extracted from the joints of Fgf2,/, and Fgf2+/+ mice following surgery and quantitatively assessed for key regulatory molecules. The effect of subcutaneous administration of recombinant FGF-2 on OA progression was assessed in Fgf2,/, mice. Results Fgf2,/, mice were morphologically indistinguishable from wild-type (WT) animals up to age 12 weeks; the cartilage thickness and proteoglycan staining were equivalent, as was the mechanical integrity of the matrix. However, Fgf2,/, mice exhibited accelerated spontaneous and surgically induced OA. Surgically induced OA in Fgf2,/, mice was suppressed to levels in WT mice by subcutaneous administration of recombinant FGF-2. Increased disease in Fgf2,/, mice was associated with increased expression of messenger RNA of Adamts5, the key murine aggrecanase. Conclusion These data identify FGF-2 as a novel endogenous chondroprotective agent in articular cartilage. [source]