Signaling Pathways
Analysis of signalling pathways during organ development
The focus of this project is the genetic and molecular control of basic processes like the regulation of dynamic cell movements and cell shape changes during organ development. As a model system we use the organogenesis of the gastrointestinal tract in Drosophila melanogaster - a process, which is based on evolutionary conserved genetic programs and molecular interactions (for further information visit
Flymove).
The gastrointestinal tract is a highly differentiated organ required for digestion, nutrient absorption and homeostasis in all multicellular organisms.
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| Proventriculus morphogenesis stained with a marker for the ectoderm (red) and a marker for the endoderm (green) at stage 10, stage 13 and stage 17 of embryogenesis, respectively. | ||
Cell movements during proventriculus development in the Drosophila embryo (Fork Head red; Defective proventriculus, green)
The functions of the digestive system require the regionalization of the gut tube along two body axes: the anterior-posterior (AP) axis and the dorso-ventral (DV) axis. Anterior/posterior-patterning serves the formation of a characteristic AP-sequence of gastrointestinal organs such as the liver and the pancreas in vertebrates or the proventriculus and the Malpighian tubules in Drosophila . Dorso/ventral patterning of the tube is required to achieve proper placement of interacting tissues such as muscle layers or nerves around the gut tube.
Several key factors of gut development, e.g. Fork Head in Drosophila and its vertebrate homolgues, the HNF3 a,b,g factors, control the specification of the gut primordia which are initially layed down as a two-dimensional sheet and subsequently transformed into a continuous threedimensional tube. Genetic disturbances of the programs controling gut development can lead to diseases like colorectal tumors (caused by a mutation in the Adenomatous Polyposis Coli (APC) gene). Since hese genetic programs share conserved signalling cascades in Drosophila and humans, Drosophila gut development can be used as a model system to get insights into the development of an evolutionary conserved organ.
Recent Projects
1. Cell biological analysis of the JAK-STAT signalling pathway during gut development
JAK-STAT signalling activity during alimentary canal development is analyzed with respect to cell specification and cell motility. Biochemical approaches are performed to identify novel molecules interacting with JAK-STAT signalling components.
2. Screen for novel genes controlling cell movements, cell polarity and cell identity within the gut epithelium
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Proventriculus of a stage 17 embryo, stained with a marker for the endoderm (green) and Kakapo antibody, a cytoskeletal adaptor protein (red). |
3. Cloning and characterization of the defective proventriculus (dve) gene in Drosophila
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Drosophila embryo, stained with a defective proventriculus antisense probe. |
4. Control of endoreduplication by Kni/Knrl is required for proper hindgut development.
published in: Fuss B, Meissner T, Bauer R, Lehmann C, Eckardt F, Hoch M. Mech Dev. 2001; 100: 15-23.5. Novel mode of Notch signalling is required to specify cell identity along the dorsal-ventral axis in the large intestine
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Dorsal-Ventral patterning in the large intestine of the Drosophila embryo (A-H). A) Anti-FasIII (green) antibody staining visualizing three distinct cell types
along the DV axis of the large intestine. |
6. defective proventriculus is required for pattern formation along the proximodistal axis, cell proliferation and formation of veins in the Drosophila wing
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| Wing disc expression of dve RNA (left panel) and Dve protein (red) and Wg protein(green) at the Dorsal/Ventral boundary of the wing (right panel) |
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The wing phenotype of dve-mutant flies. Wildtype, left; dve mutant right. In dve mutants, the longitudinal veins 2 and 5 are interrupted, the wing is smaller than the wild-type wing and the distance between the arrowhead in the PW and that at the anterior cross-vein is strongly reduced in comparison with the normal wing. published in: Kolzer S, Fuss B, Hoch M. and Klein T. Development 2003; 130:4135-47. |
Project group
Publications
Fuss, B., Josten, F., Feix, M., Meissner, T. and Hoch, M. Cooperation of JAK/STAT and Notch signalling in the Drosophila foregut. Developmental Biology 2004; 267: 181-189.
Fuss, B., Josten, F., Feix, M. and Hoch, M. Cell movements controlled by the Notch signalling cascade during foregut development in Drosophila. Development 2004; 131:1587-95.
Kölzer. S, Fuss, B., Hoch, M. and Klein, T. (2003). The homeobox transcription factor encoded by the defective ventriculus (dve) gene is required for pattern formation along the proximo-distal axis of the Drosophila wing. Development, Development 2003; 130:4135-47.
Fuss, B., Josten F., Feix, M. and Hoch M . Localized changes of cell shapes: controlling cell movements within a tubular epithelium. E. J. Cell Biol. 2003; Suppl. 53: 122.
Fuss, B. and Hoch, M. Studying the molecular basis of differentiation and movements of polarized epithelial cells: The Drosophila gastro-intestinal tract. Zellbiologie aktuell 2003; 1: 9-12.
Bauer, R., Lehmann, C., Fuss, B., Eckardt, F. and Hoch, M. (2002). The Drosophila gap junction channel gene innexin 2 controls foregut development in response to Wingless signalling. J. Cell Sci. 115, 1859-1867.
Fuss, B. and Hoch, M. (2002). Notch signaling controls cell fate specification along the dorso-ventral axis of the Drosophila gut. Curr. Biol. 12, 171-179.
Fuss, B., Meißner, T., Bauer, R., Lehmann, C., Eckardt, F. and Hoch, M. (2001). Control of endoreduplication domains in the Drosophila gut by the knirps and knirps-related genes. Mech. Dev. 100, 15-23.
Fuss, B. and Hoch, M. (1998). Drosophila endoderm development requires a novel homeobox gene which is a target of Wingless and Dpp signalling. Mech. Dev., 79, 83-97.
