Characterization of signal transduction components between cells: the Drosophila melangogaster X-chromosomal genes trol and tao

1. Neuroblasten sind die Stammzellen des Nervensystems von Drosophila. Ihre Proliferation wird über den Zellzyklus reguliert. Verschiedene Gene wurden identifiziert, welche die Proliferation von Neuroblasten kontrollieren. Dazu zählen anachronism (ana), even skipped (eve) und terribly reduced optic lobes (trol). Eve reguliert die Produktion eines Faktors, der die Proliferation von Neuroblasten der optischen Loben stimuliert. Das sezernierte Protein Ana hingegen reprimiert die Proliferation dieser Neuroblasten. Diese Repression wird von Trol umgangen oder inaktiviert. Wie wir zeigen codiert trol für Drosophila-Perlecan, ein Protein der extrazellulären Matrix. Unsere Ergebnisse deuten darauf hin, daß Trol in der extrazellulären Matrix Signalmoleküle bindet, speichert und abgibt. Es ist somit an der Kontrolle der Neuroblastenproliferation beteiligt. 2. Die Alzheimersche Krankheit (AK) und verwandte Tauopathien sind neurodegenerative Krankheiten, deren Kennzeichen das Vorhandensein von anormal phosphoryliertem Mikrotubuli-assoziiertem Protein Tau (MAPT) und dessen Aggregation ist. Eines der Schlüsselereignisse der AK ist die Phosphorylierung von MAPT, über die Kontrolle dieser Phosphorylierung ist jedoch wenig bekannt. Die Familie der MARK/Par1-Kinasen phosphorylieren MAPT, hirachisch übergeordnete Aktivatoren MARK/Par1 sind jedoch nicht bekannt. Für die Serin/Threonin-Kinase MARKK konnte in vitro gezeigt werden, daß sie MARK aktiviert, was zu einer MAPT Phosphorylierung führt. Darüber hinaus konnte in Zellkulturexperimenten eine Phosphorylierung von MEKs der MAPK-Kaskade durch Tao1 nachgewiesen werden. Daten bezüglich der Funktion von Tao1/MARKK auf organismischer Ebene sind nicht bekannt. Wir haben das Tao1/MARKK homologe Gen von Drosophila (dtao) identifiziert und dessen Funktion analysiert. Wir zeigen, daß dTao in vivo die MAPT-vermittelte Toxizität verstärkt. Darüber hinaus wird eine Involvierung von dTao an der Signaltransduktion der MAPK-Kaskade nachgewiesen.1. Neuroblasts are the stem cells of the Drosophila nervous system. Their proliferation is controlled through cell cycle. Several genes have been identified that control neuroblast proliferation, including anachronism (ana), even skipped (eve) and terribly reduced optic lobes (trol). Eve controls the production of a transacting factor that stimulates proliferation of quiescent optic lobe neuroblasts. The secreted protein Ana represses the proliferation of these neuroblasts. This repression is inactivated or bypassed by trol. Here, we show that trol codes for Drosophila Perlecan, a protein of the extracellular matrix. Our results suggest that Trol acts in the extracellular matrix where it binds, stores, and sequesters external signals. It thereby participates in the control of neuroblast proliferation. 2. Alzheimers disease (AD) and related tauopathies are common neurodegenerative disorders. The hallmark of these disorders is the presence of abnormally phosphorylated microtuble-binding protein Tau (MAPT) and its aggregation. Although phosphorylation of MAPT is a critical event in the progression of AD, the control mechanisms underlying MAPT phosphorylation are largely unknown. The MARK/Par1 family of kinases have been shown to phosphorylate MAPT, but upstream activators of these kinases are still unknown. Recently MARKK/Tao1 a serine/threonine kinase was shown to activate MARKs leading to MAPT phosphorylation in vitro. Cellculture experiments showed in addition that Tao1 phosphorylates MEKs of the MAPK cascade. Data concerning the function of Tao1/MARKK on organismic level are still elusive. We have identified the Drosophia homologue of Tao1/MARKK and analyzed its function. Here we show that dTao is involved in MAPT-induced toxicity in vivo. In addition we show that dTao is involved in signaling through the MAPK cascade

Prospectus, July 10, 2008

https://spark.parkland.edu/prospectus_2008/1014/thumbnail.jp

Prospectus, February 21, 2008

https://spark.parkland.edu/prospectus_2008/1003/thumbnail.jp

Prospectus, November 8, 2007

https://spark.parkland.edu/prospectus_2007/1024/thumbnail.jp

Targeted Ablation of Oligodendrocytes Triggers Axonal Damage

Glial dysfunction has been implicated in a number of neurodegenerative diseases. In this study we investigated the consequences of glial and oligodendrocyte ablation on neuronal integrity and survival in Drosophila and adult mice, respectively. Targeted genetic ablation of glia was achieved in the adult Drosophila nervous system using the GAL80-GAL4 system. In mice, oligodendrocytes were depleted by the injection of diphtheria toxin in MOGi-Cre/iDTR double transgenic animals. Acute depletion of oligodendrocytes induced axonal injury, but did not cause neuronal cell death in mice. Ablation of glia in adult flies triggered neuronal apoptosis and resulted in a marked reduction in motor performance and lifespan. Our study shows that the targeted depletion of glia triggers secondary neurotoxicity and underscores the central contribution of glia to neuronal homeostasis. The models used in this study provide valuable systems for the investigation of therapeutic strategies to prevent axonal or neuronal damage

Prospectus, April 17, 2008

https://spark.parkland.edu/prospectus_2008/1010/thumbnail.jp

Evidence for Glass–glass Interfaces in a Columnar Cu–Zr Nanoglass

Comprehensive analyses of the atomic structure using advanced analytical transmission electron microscopy-based methods combined with atom probe tomography confirm the presence of distinct glass–glass interfaces in a columnar Cu-Zr nanoglass synthesized by magnetron sputtering. These analyses provide first-time in-depth characterization of sputtered film nanoglasses and indicate that glass–glass interfaces indeed present an amorphous phase with reduced mass density as compared to the neighboring amorphous regions. Moreover, dedicated analyses of the diffusion kinetics by time-of-flight secondary ion mass spectroscopy (ToF SIMS) prove significantly enhanced diffusivity, suggesting fast transport along the low density glass–glass interfaces. The present results further indicate that sputter deposition is a feasible technique for reliable production of nanoglasses and that some of the concepts proposed for this new class of glassy materials are applicable

Prospectus, November 19, 2007

https://spark.parkland.edu/prospectus_2007/1025/thumbnail.jp

A Synthetic Genetic Edge Detection Program

SummaryEdge detection is a signal processing algorithm common in artificial intelligence and image recognition programs. We have constructed a genetically encoded edge detection algorithm that programs an isogenic community of E. coli to sense an image of light, communicate to identify the light-dark edges, and visually present the result of the computation. The algorithm is implemented using multiple genetic circuits. An engineered light sensor enables cells to distinguish between light and dark regions. In the dark, cells produce a diffusible chemical signal that diffuses into light regions. Genetic logic gates are used so that only cells that sense light and the diffusible signal produce a positive output. A mathematical model constructed from first principles and parameterized with experimental measurements of the component circuits predicts the performance of the complete program. Quantitatively accurate models will facilitate the engineering of more complex biological behaviors and inform bottom-up studies of natural genetic regulatory networks