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Heidelberg, Germany

Pinto P.B.,University of Seville | Pinto P.B.,Center for Organismal Studies | Espinosa-Vazquez J.M.,University of Seville | Rivas M.iL.i,University of Seville | Hombria J.C.-G.,University of Seville
PLoS Genetics | Year: 2015

Organogenesis is controlled by gene networks activated by upstream selector genes. During development the gene network is activated stepwise, with a sequential deployment of successive transcription factors and signalling molecules that modify the interaction of the elements of the network as the organ forms. Very little is known about the steps leading from the early specification of the cells that form the organ primordium to the moment when a robust gene network is in place. Here we study in detail how a Hox protein induces during early embryogenesis a simple organogenetic cascade that matures into a complex gene network through the activation of feedback and feed forward interaction loops. To address how the network organization changes during development and how the target genes integrate the genetic information it provides, we analyze in Drosophila the induction of posterior spiracle organogenesis by the Hox gene Abdominal-B (Abd-B). Initially, Abd-B activates in the spiracle primordium a cascade of transcription factors and signalling molecules including the JAK/STAT signalling pathway. We find that at later stages STAT activity feeds back directly into Abd-B, initiating the transformation of the Hox cascade into a gene-network. Focusing on crumbs, a spiracle downstream target gene of Abd-B, we analyze how a modular cis regulatory element integrates the dynamic network information set by Abd-B and the JAK/STAT signalling pathway during development. We describe how a Hox induced genetic cascade transforms into a robust gene network during organogenesis due to the repeated interaction of Abd-B and one of its targets, the JAK/STAT signalling cascade. Our results show that in this network STAT functions not just as a direct transcription factor, but also acts as a "counter-repressor", uncovering a novel mode for STAT directed transcriptional regulation. © 2015 Pinto et al.

Althoff F.,University of Heidelberg | Althoff F.,Max Planck Institute for Chemistry | Benzing K.,University of Heidelberg | Comba P.,University of Heidelberg | And 5 more authors.
Nature Communications | Year: 2014

Methane in the environment is produced by both biotic and abiotic processes. Biomethanation involves the formation of methane by microbes that live in oxygen-free environments. Abiotic methane formation proceeds under conditions at elevated temperature and/or pressure. Here we present a chemical reaction that readily forms methane from organosulphur compounds under highly oxidative conditions at ambient atmospheric pressure and temperature. When using iron(II/III), hydrogen peroxide and ascorbic acid as reagents, S-methyl groups of organosulphur compounds are efficiently converted into methane. In a first step, methyl sulphides are oxidized to the corresponding sulphoxides. In the next step, demethylation of the sulphoxide via homolytic bond cleavage leads to methyl radical formation and finally to methane in high yields. Because sulphoxidation of methyl sulphides is ubiquitous in the environment, this novel chemical route might mimic methane formation in living aerobic organisms. © 2014 Macmillan Publishers Limited. All rights reserved.

Walentek P.,University of Hohenheim | Beyer T.,University of Hohenheim | Thumberger T.,University of Hohenheim | Thumberger T.,Center for Organismal Studies | And 2 more authors.
Cell Reports | Year: 2012

Most vertebrate embryos break symmetry by a cilia-driven leftward flow during neurulation. In the frog . Xenopus asymmetric expression of the ion pump . ATP4a was reported at the 4-cell stage. The " ion-flux" model postulates that symmetry is broken flow-independently through an ATP4-generated asymmetric voltage gradient that drives serotonin through gap junctions to one side of the embryo. Here, we show that . ATP4a is symmetrically expressed. Gene knockdown or pharmacological inhibition compromised organ situs, asymmetric marker gene expression, and leftward flow. The gastrocoel roof plate (GRP), where flow in frog occurs, revealed fewer, shortened, and misaligned cilia. . Foxj1, a master control gene of motile cilia, was downregulated in the superficial mesoderm, from which the GRP develops. Specifically, ATP4 was required for Wnt/β-catenin-regulated . Foxj1 induction and Wnt/PCP-dependent cilia polarization. Our work argues for evolutionary conservation of symmetry breakage in the vertebrates.

Mazaheri F.,Developmental Biology Unit | Breus O.,Developmental Biology Unit | Durdu S.,Cell biology and biophysics unit | Haas P.,Center for Organismal Studies | And 4 more authors.
Nature Communications | Year: 2014

The removal of dying neurons by microglia has a key role during both development and in several diseases. To date, little is known about the cellular and molecular processes underlying neuronal engulfment in the brain. Here we took a live imaging approach to quantify neuronal cell death progression in embryonic zebrafish brains and studied the response of microglia. We show that microglia engulf dying neurons by extending cellular branches that form phagosomes at their tips. At the molecular level we found that microglia lacking the phosphatidylserine receptors BAI1 and TIM-4, are able to recognize the apoptotic targets but display distinct clearance defects. Indeed, BAI1 controls the formation of phagosomes around dying neurons and cargo transport, whereas TIM-4 is required for phagosome stabilization. Using this single-cell resolution approach we established that it is the combined activity of BAI1 and TIM-4 that allows microglia to remove dying neurons. © 2014 Macmillan Publishers Limited. All rights reserved.

Yokoyama H.,University of Heidelberg | Koch B.,European Molecular Biology Laboratory | Walczak R.,European Molecular Biology Laboratory | Ciray-Duygu F.,University of Heidelberg | And 4 more authors.
Nature communications | Year: 2014

The GTP-bound form of the Ran GTPase (RanGTP), produced around chromosomes, drives nuclear envelope and nuclear pore complex (NPC) re-assembly after mitosis. The nucleoporin MEL-28/ELYS binds chromatin in a RanGTP-regulated manner and acts to seed NPC assembly. Here we show that, upon mitotic NPC disassembly, MEL-28 dissociates from chromatin and re-localizes to spindle microtubules and kinetochores. MEL-28 directly binds microtubules in a RanGTP-regulated way via its C-terminal chromatin-binding domain. Using Xenopus egg extracts, we demonstrate that MEL-28 is essential for RanGTP-dependent microtubule nucleation and spindle assembly, independent of its function in NPC assembly. Specifically, MEL-28 interacts with the γ-tubulin ring complex and recruits it to microtubule nucleation sites. Our data identify MEL-28 as a RanGTP target that functions throughout the cell cycle. Its cell cycle-dependent binding to chromatin or microtubules discriminates MEL-28 functions in interphase and mitosis, and ensures that spindle assembly occurs only after NPC breakdown.

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