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Embryonic Lethal (embryonic + lethal)
Selected AbstractsThe commonly used marker ELAV is transiently expressed in neuroblasts and glial cells in the Drosophila embryonic CNSDEVELOPMENTAL DYNAMICS, Issue 12 2007Christian Berger Abstract Glial cells in the Drosophila embryonic nervous system can be monitored with the marker Reversed-polarity (Repo), whereas neurons lack Repo and express the RNA-binding protein ELAV (Embryonic Lethal, Abnormal Vision). Since the first description of the ELAV protein distribution in 1991 (Robinow and White), it is believed that ELAV is an exclusive neuronal and postmitotic marker. Looking at ELAV expression, we unexpectedly observed that, in addition to neurons, ELAV is transiently expressed in embryonic glial cells. Furthermore, it is transiently present in the proliferating longitudinal glioblast, and it is transcribed in embryonic neuroblasts. Likewise, elav -Gal4 lines, which are generally used as postmitotic neuronal driver lines, show expression in neural progenitor cells and nearly all embryonic glial cells. Thus, in the embryo, elav can no longer be considered an exclusive marker or driver for postmitotic neurons. elav loss-of-function mutants show no obvious effects on the number and pattern of embryonic glia. Developmental Dynamics 236:3562,3568, 2007. © 2007 Wiley-Liss, Inc. [source] PDGFR-, signaling is critical for tooth cusp and palate morphogenesisDEVELOPMENTAL DYNAMICS, Issue 1 2005Xun Xu Abstract Platelet-derived growth factor receptor alpha (PDGFR-,) and PDGF ligands are key regulators for embryonic development. Although Pdgfr, is spatially expressed in the cranial neural crest (CNC)-derived odontogenic mesenchyme, mice deficient for Pdgfr, are embryonic lethal, making it impossible to investigate the functional significance of PDGF signaling in regulating the fate of CNC cells during tooth morphogenesis. Taking advantage of the kidney capsule assay, we investigated the biological function of PDGF signaling in regulating tooth morphogenesis. Pdgfr, and Pdgfa are specifically and consistently expressed in the CNC-derived odontogenic mesenchyme and the dental epithelium, respectively, throughout all stages of tooth development, suggesting a paracrine function of PDGF signaling in regulating tooth morphogenesis. Highly concentrated expression patterns of Pdgfr, and Pdgfa are associated with the developing dental cusp, suggesting possible functional importance of PDGF signaling in regulating cusp formation. Loss of the Pdgfr, gene does not affect proper odontoblasts proliferation and differentiation in the CNC-derived odontogenic mesenchyme but perturbs the formation of extracellular matrix and the organization of odontoblast cells at the forming cusp area, resulting in dental cusp growth defect. Pdgfr,,/, mice have complete cleft palate. We show that the cleft palate in Pdgfr, mutant mice results from an extracellular matrix defect within the CNC-derived palatal mesenchyme. The midline epithelium of the mutant palatal shelf remains functionally competent to mediate palatal fusion once the palatal shelves are placed in close contact in vitro. Collectively, our data suggests that PDGFR, and PDGFA are critical regulators for the continued epithelial,mesenchymal interaction during tooth and palate morphogenesis. Disruption of PDGFR, signaling disturbs the growth of dental cusp and interferes with the critical extension of palatal shelf during craniofacial development. Developmental Dynamics 232:75,84, 2005. © 2004 Wiley-Liss, Inc. [source] GANP suppresses DNA recombination, measured by direct-repeat ,-galactosidase gene construct, but does not suppress the type of recombination applying to immunoglobulin genes in mammalian cellsGENES TO CELLS, Issue 10 2007Mikoto Yoshida Immunoglobulin V-region somatic hypermutation and C-region class-switch recombination are initiated by activation-induced cytidine deaminase (AID) in B-cells. AID-induced DNA damage at the immunoglobulin S-region is known to be repaired by non-homologous end-joining, but repair mechanisms at the V-region remain to be elucidated. In Saccharomyces cerevisiae, DNA homologous recombination is regulated by the expression of Sac3, involved in actin assembly, cell cycle transition and mRNA metabolism. Here, we demonstrate that the Sac3-homologue GANP suppresses DNA recombination in a direct-repeat ,-galactosidase gene construct in mammalian cells. Homozygous ganp gene knockout is embryonic lethal in mice. Embryonic fibroblasts immortalized from hetero-deficient ganp+/, mice showed more DNA recombination than wild-type. In contrast, over-expression of GANP suppressed either spontaneous DNA recombination or that caused by the introduction of aid cDNA into NIH3T3 cells (susceptible to I-sceI restriction enzyme cleavage but not to RAG-mediated immunoglobulin gene recombination). GANP suppresses the DNA recombination not only on the extrachromosomal DNA construct but also on the integrated DNA. The Sac3-homology portion is necessary for the suppressive activity, but the truncated carboxyl terminal MCM3-binding/acetylating region adversely augmented DNA recombination, acting as a dominant negative form. Expression of full-length GANP is critical for suppression of DNA hyper-recombination in mammalian cells. [source] The A-type cyclins and the meiotic cell cycle in mammalian male germ cellsINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 4 2004Debra J. Wolgemuth Summary There are two mammalian A-type cyclins, cyclin Al and A2. While cyclin A1 is limited to male germ cells, cyclin A2 is widely expressed. Cyclin A2 promotes both Gl/S and G2/M transitions in somatic cells and cyclin A2-deficient mice are early embryonic lethal. We have shown that cyclin Al is essential for passage of spermatocytes into meiosis I (MI) by generating mice null for the cyclin A1 gene Ccna1. Both Ccna1,/, males and females were healthy but the males were sterile because of a cell cycle arrest before MI. This arrest was associated with desynapsis abnormalities, low M-phase promoting factor activity, and apoptosis. We have now determined that human cyclin A1 is expressed in similar stages of spermatogenesis and are exploring its role in human male infertility and whether it may be a novel target for new approaches for male contraception. [source] MLL: How complex does it get?JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2005Relja Popovic Abstract The mixed lineage leukemia (MLL) gene encodes a very large nuclear protein homologous to Drosophila trithorax (trx). MLL is required for the proper maintenance of HOX gene expression during development and hematopoiesis. The exact regulatory mechanism of HOX gene expression by MLL is poorly understood, but it is believed that MLL functions at the level of chromatin organization. MLL was identified as a common target of chromosomal translocations associated with human acute leukemias. About 50 different MLL fusion partners have been isolated to date, and while similarities exist between groups of partners, there exists no unifying property shared by all the partners. MLL gene rearrangements are found in leukemias with both lymphoid and myeloid phenotypes and are often associated with infant and secondary leukemias. The immature phenotype of the leukemic blasts suggests an important role for MLL in the early stages of hematopoietic development. Mll homozygous mutant mice are embryonic lethal and exibit deficiencies in yolk sac hematopoiesis. Recently, two different MLL-containing protein complexes have been isolated. These and other gain- and loss-of-function experiments have provided insight into normal MLL function and altered functions of MLL fusion proteins. This article reviews the progress made toward understanding the function of the wild-type MLL protein. While many advances in understanding this multifaceted protein have been made since its discovery, many challenging questions remain to be answered. © 2005 Wiley-Liss, Inc. [source] Rac1 and Rac2 GTPases in haematopoiesisBIOESSAYS, Issue 3 2004Victoria J. Weston The highly homologous Rac1 and Rac2 GTPases are co-expressed in cells of haematopoietic origin and are likely to show some functional redundancy. While disruption of the Rac2 gene in mice has provided insight into some of its functions, Rac1 null mice are embryonic lethal and only recently has conditional gene disruption been possible. Consequently, two articles1,2 have recently elucidated some overlapping and unique key roles of Rac1 and Rac2 in haematopoietic processes including specialized roles in innate and humoral immunity. BioEssays 26:221,224, 2004. © 2004 Wiley Periodicals, Inc. [source] | ||||||||||