A5043406126- Developmental Biology and Gene Regulation
- Neurobiology and Insect Physiology Research
- Physiological and biochemical adaptations
- Axon Guidance and Neuronal Signaling
- Microtubule and mitosis dynamics
- Hippo pathway signaling and YAP/TAZ
- Neurogenesis and neuroplasticity mechanisms
- Invertebrate Immune Response Mechanisms
- RNA Research and Splicing
- Genetics, Aging, and Longevity in Model Organisms
- Pluripotent Stem Cells Research
- Protist diversity and phylogeny
- Genomics and Chromatin Dynamics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Spaceflight effects on biology
- Zebrafish Biomedical Research Applications
- Plant Molecular Biology Research
- Nerve injury and regeneration
- Neuroscience, Education and Cognitive Function
- Cancer, Hypoxia, and Metabolism
- Cell Image Analysis Techniques
- Cancer-related gene regulation
- Retinoids in leukemia and cellular processes
- Hereditary Neurological Disorders
- MicroRNA in disease regulation
University of Fribourg
2012-2024
University of Cambridge
2005-2018
The Gurdon Institute
2005-2018
Wellcome Trust
2005-2009
University of Basel
2000-2004
Roche (Switzerland)
2000
Technical University of Munich
1981
Cell-type-specific transcriptional profiling often requires the isolation of specific cell types from complex tissues. We have developed "TaDa," a technique that enables cell-specific without isolation. TaDa permits genome-wide DNA- or chromatin-binding proteins sorting, fixation, affinity purification. The method is simple, sensitive, highly reproducible, and transferable to any model system. show can be used identify transcribed genes in cell-type-specific manner with considerable temporal...
Abstract Background The choice of a stem cell to divide symmetrically or asymmetrically has profound consequences for development and disease. Unregulated symmetric division promotes tumor formation, whereas inappropriate asymmetric affects organ morphogenesis. Despite its importance, little is known about how spindle positioning regulated. In some tissues fate appears dictate the type division, in other it thought that stochastic variation position dictates subsequent sibling fate. Results...
The proper balance between symmetric and asymmetric stem cell division is crucial both to maintain a population of cells prevent tumorous overgrowth. Neural in the Drosophila optic lobe originate within polarised neuroepithelium, where they divide symmetrically. Neuroepithelial are transformed into asymmetrically dividing neuroblasts precisely regulated fashion. This fate transition highly reminiscent switch from neuroepithelial radial glial developing mammalian cerebral cortex. To identify...
Centrosome asymmetry has been implicated in stem cell fate maintenance both flies and vertebrates, but the underlying molecular mechanisms are incompletely understood. Here, we report that loss of CG7337, fly ortholog WDR62, compromises interphase centrosome neural cells (neuroblasts). Wdr62 maintains an active microtubule-organizing center (MTOC) by stabilizing microtubules (MTs), which necessary for sustained recruitment Polo/Plk1 to pericentriolar matrix (PCM) downregulation...
After a peripheral nerve lesion, distal ends of injured axons disintegrate into small fragments that are subsequently cleared by Schwann cells and later macrophages. Axonal debris clearing is an early step the repair process facilitates regeneration. We show here promote cut axon disintegration for timely clearing. By combining cell-based in vivo models lesion with mouse genetics, we this mechanism induced axons, which signal to through PlGF mediating activation upregulation VEGFR1 cells. In...
In Drosophila, the glial cells missing (gcm) gene encodes a transcription factor that controls determination of versus neuronal fate. gcm mutants, presumptive are transformed into neurons and, conversely, when is ectopically misexpressed, become glia. Although thought to initiate cell development through its action on downstream genes execute differentiation program, little known about identity these genes. To identify in comprehensive manner, we used genome-wide oligonucleotide arrays...
The pathogenesis of peripheral neuropathies in adults is linked to maintenance mechanisms that are not well understood. Here, we elucidate a novel critical mechanism for Schwann cell (SC)–axon interaction. Using mouse genetics, ablation the transcriptional regulators histone deacetylases 1 and 2 (HDAC1/2) adult SCs severely affected paranodal nodal integrity led demyelination/remyelination. Expression levels HDAC1/2 target gene myelin protein zero (P0) were reduced by half, accompanied...
Cells experience different oxygen concentrations depending on location, organismal developmental stage, and physiological or pathological conditions. Responses to reduced levels (hypoxia) rely the conserved Hypoxia-Inducible Factor 1 (HIF-1). Understanding tissue-specific responses changing has been limited by lack of adequate tools for monitoring HIF-1 in vivo. To visualise analyse dynamics Drosophila, we used a hypoxia biosensor consisting GFP fused oxygen-dependent degradation domain...
Embryonic development in Drosophila is characterized by an early phase during which a cellular blastoderm formed and gastrulation takes place, later postgastrulation key morphogenetic processes such as segmentation organogenesis occur. We have focused on this embryogenesis with the goal of obtaining comprehensive analysis zygotic gene expression that occurs under normal altered environmental conditions. For this, functional genomic approach to has been developed uses high-density...
Abstract Background The production of new neurons during adulthood and their subsequent integration into a mature central nervous system have been shown to occur in all vertebrate species examined date. However, the situation insects is less clear and, particular, it has reported that there no proliferation Drosophila adult brain. Results We report here, using clonal analysis 5'-bromo-2'-deoxyuridine (BrdU) labelling, cell does majority clones cluster on ventrolateral side antennal lobes, as...
Lasting changes in gene expression are critical for the formation of long-term memories (LTMs), depending on conserved CrebB transcriptional activator. While requirement distinct neurons defined circuits different learning and memory phases have been studied detail, only little is known regarding regulatory that occur within these neurons. We here use fruit fly as powerful model system to study neural CrebB-dependent appetitive olfactory LTM. edited locus create a GFP-tagged conditional...
Hox genes encode evolutionarily conserved transcription factors involved in the specification of segmental identity during embryonic development. This is thought to be directed by differential gene action, based on spatiotemporal expression patterns, protein sequence differences, interactions with co-factors and regulation specific downstream genes. During development Drosophila brain, labial required for regionalized tritocerebral neuromere; absence labial, cells this brain region do not...
Neural stem cells generate all of the neurons and glial in central nervous system, both during development adult to maintain homeostasis. In Drosophila optic lobe, neuroepithelial progress through two transient progenitor states, PI PII, before transforming into neuroblasts. Here we analyse role Notch signalling transition from We observed dynamic regulation signalling: strong activity progenitors, low PII increased after neuroblast transformation. Ectopic expression ligand Delta induced...
Mutations and gene expression alterations in brain tumors have been extensively investigated, however the causes of tumorigenesis are largely unknown. Animal models necessary to correlate altered transcriptional activity tumor phenotype better understand how these cause malignant growth. In order gain insights into vivo associated with a tumor, we carried out genome-wide microarray analyses an adult Drosophila caused by homozygous mutation suppressor (brat). Two independent studies using two...
ABSTRACT Environmental factors such as the availability of oxygen are instructive cues that regulate stem cell maintenance and differentiation. We used a genetically encoded biosensor to monitor hypoxic state neural cells in larval brain Drosophila. The reveals compartment cell-type specific levels hypoxia. values correlate with differential tracheolation is observed throughout development between central optic lobe. Neural both compartments show strongest hypoxia response while intermediate...
Abstract In Drosophila, most neurogenetic research is carried out in vivo. Mammalian demonstrates that primary cell culture techniques provide a powerful model to address autonomous and non-autonomous processes outside their endogenous environment. We developed system Drosophila using wildtype genetically manipulated neural tissue for long-term observations. assessed the molecular identity of distinct types by immunolabeling expressed fluorescent markers. monitored mitotic activity cultures...