Luschnig, Stefan, Prof. Dr. rer. nat.
Westfälische Wilhelms-Universität Münster
Institute for Zoophysiology
Institute for Neuro- and Behavioural Biology
Tel: + 49 - 251 83 2 1696
Fax: + 49 - 251 83 2 4686
Luschnig, Stefan, Prof. Dr. rer. nat.
1990-1996 Studium der Biologie: Universität Erlangen
1996-2000 Promotion: Max-Planck Institut für Entwicklungsbiologie Tübingen
2000-2004 Postdoctoral research associate: Stanford University School of Medicine /Howard Hughes Medical Institute, USA
2004-2007 Forschungsgruppenleiter am Lehrstuhl für Genetik, Universität Bayreuth
2007-2015 Forschungsgruppenleiter am Institut für Molekulare Biologie, Zürich, Schweiz
2015 - Professor für “Morphogenese Tubuläre Organe“ an der WWU Münster / Exzellenzcluster “Cells in Motion“ (CiM)
- Molekulare Genetik
- Zelluläre und molekulare Mechanismen der Morphogenese in Epithelien
- Dynamik des intrazellulären Membran- und Proteintransports
- Aufbau und Funktion von epithelialen Barrieren
Our research addresses developmental, cellular, molecular, and functional aspects of epithelial biology. In particular, we investigate how the dimensions and shapes of epithelial tubes are controlled. The correct size and shape of tubular epithelia is critical for the function of vital organs, such as our lungs, kidneys, and blood vessels. However, it is not understood how epithelial cells measure, adjust, and maintain defined tubular dimensions. To address these fundamental questions, we use primarily the tracheal (respiratory) system in Drosophila melanogaster as an accessible and comparatively simple model. We apply a combination of molecular, genetic, cell biological, and quantitative imaging approaches to analyze the behavior of cells and tissues during tube morphogenesis.
Cell behavior and tissue mechanics in cylindrical epithelia
We defined distinct cellular processes that independently control tracheal tube elongation and diametric expansion. We showed that the conserved tyrosine kinase Src42 induces axially polarized cell shape changes that drive tracheal tube elongation (Förster and Luschnig 2012). Conversely, diametric tube expansion is controlled independently of Src42 by apical secretion. Secretory activity drives luminal expansion in a cell-autonomous fashion by promoting apical membrane growth and cell flattening. A cell-intrinsic program, rather than non-autonomous extrinsic cues, controls the dimensions of tracheal tubes. Our findings provide a framework to dissect the control of tube dimensions at the cellular and molecular level. We ask how cells sense and respond to mechanical forces, such as anisotropic tissue tension, which are imposed by the cylindrical geometry of tubular epithelia. To analyze cellular behavior during tracheal tube expansion, we employ genetic labeling and imaging tools. We also aim to measure and manipulate mechanical forces during tube morphogenesis to experimentally test predictions derived from theoretical models.
Intracellular membrane dynamics during epithelial tube fusion
We study how tubular networks develop from initially separate units. In the vascular system separate endothelial sprouts fuse to build tubular bridges (anastomoses). Despite the fundamental role of this process in organogenesis and pathology, the mechanisms that govern epithelial tube fusion are not well understood. Tube fusion events resembling vascular anastomosis formation also occur during development of the tracheal system. Tube fusion involves directed migration of cells towards the fusion point, formation of a new cell-cell junction, and finally the connection of adjacent tubes. We aim to understand the mechanism of membrane fusion during the connection of tracheal tubes. We use in vivo cell labeling techniques combined with high-resolution light and electron microscopy to define the intermediates of the fusion process at the cellular and ultrastructural level. To identify new components of the underlying cellular machinery, we characterize fusion-defective mutants, which we isolated in genetic screens (Caviglia and Luschnig 20143. Answering basic questions about lumen formation and conversion of cellular topology in the Drosophila tracheal tube fusion model can provide a conceptual framework to help elucidate similar processes, such as vascular anastomosis and pronephric duct fusion, in more complex vertebrate systems.
Formation and function of epithelial tricellular junctions
We investigate the assembly and function of epithelial barriers. Tight junctions in vertebrates and septate junctions in invertebrates form diffusion barriers by sealing the paracellular space between plasma membranes of neighboring cells. Junctions between two adjacent cells (bicellular junctions) have been intensely studied and most of their components are known. However, sealing the epithelium at sites of contact between three cells requires specialized tricellular junctions (TCJs). Despite their fundamental role in epithelial biology, TCJs have received little attention and are poorly described in terms of their structure, composition, and the dynamics of their assembly and maintenance. We characterized Anakonda (Aka), a new TCJ protein with an unusual triple-repeat structure, which plays a key role in TCJ assembly and function (Byri et al. 2015).
Please contact us for further information on individual projects in the lab.
Caviglia, S., Brankatschk, M., Fischer, E., Eaton, S., and Luschnig, S. (2016). Staccato/unc13-4 controls secretory lysosome-mediated lumen fusion during epithelial tube anastomosis. Nature Cell Biology, 18(7): 727–739.
Misra, T., Baccino Calace, M., Meyenhofer, T., Rodriguez-Crespo, D., Akarsu, H., Armenta-Calderón, R., Gorr, T.A., Frei, C., Cantera, R., Egger, B., and Luschnig, S. (2016). A genetically encoded biosensor for visualizing hypoxia responses in vivo. Biology Open 6(2): 296-304
Byri, S., Misra, T., Syed, Z.A., Bätz, T., Shah, J., Boril, L., Glashauser, J., Aegerter-Wilmsen, T., Matzat, T., Moussian, B., Uv, A., and Luschnig, S. (2015). The triple-repeat protein Anakonda controls epithelial tricellular junction formation in Drosophila. Developmental Cell, in press.
Förster, D. and Luschnig, S. (2012). Src42A-dependent polarized cell shape changes mediate epithelial tube elongation in Drosophila. Nature Cell Biology 14(5): 526–534.
- 10.1242/dev.144535. . ‘Faithful mRNA splicing depends on the Prp19 complex subunit faint sausage and is required for tracheal branching morphogenesis in Drosophila.’ Development (Cambridge) 144, No. 4: 657-663. doi:
- . . ‘A genetically encoded biosensor for visualizing hypoxia responses in vivo.’ Biology Open 6, No. 2: bio.018226. doi: 10.1242/bio.018226.
- . . ‘Rabs on the fly: Functions of Rab GTPases during development.’ Small GTPases 0: 1-10.
- 10.1371/journal.pgen.1006073. . ‘miR-190 enhances HIF-dependent responses to hypoxia in Drosophila by inhibiting the prolyl-4-hydroxylase Fatiga.’ PLoS Genetics 12. doi:
- 10.1038/ncb3374. . ‘Staccato/Unc-13-4 controls secretory lysosome-mediated lumen fusion during epithelial tube anastomosis.’ Nature Cell Biology 18, No. 7: 727-739. doi:
- 10.1016/j.devcel.2015.03.023. . ‘The Triple-Repeat Protein Anakonda Controls Epithelial Tricellular Junction Formation in Drosophila.’ Developmental Cell 33, No. 5: 535-548. doi:
- 10.1242/dev.102160. . ‘The transmembrane protein Macroglobulin complement-related is essential for septate junction formation and epithelial barrier function in Drosophila.’ Development (Cambridge) 141, No. 4: 899-908. doi:
- 10.1016/j.semcdb.2014.03.018. . ‘Tube fusion: Making connections in branched tubular networks.’ Seminars in Cell and Developmental Biology 31, No. null: 82-90. doi:
- 10.1016/j.yexcr.2013.09.010. . ‘Luminal matrices: An inside view on organ morphogenesis.’ Experimental Cell Research 321, No. 1: 64-70. doi:
- 10.1242/dev.087874. . ‘The ETS domain transcriptional repressor anterior open inhibits map kinase and wingless signaling to couple tracheal cell fate with branch identity.’ Development (Cambridge) 140, No. 6: 1240-1249. doi:
- 10.1038/ncb2456. . ‘Src42A-dependent polarized cell shape changes mediate epithelial tube elongation in Drosophila.’ Nature Cell Biology 14, No. 5: 526-534. doi:
- 10.1242/jcs.096263. . ‘The Drosophila Sec7 domain guanine nucleotide exchange factor protein Gartenzwerg localizes at the cis-Golgi and is essential for epithelial tube expansion.’ Journal of Cell Science 125, No. 5: 1318-1328. doi:
- 10.1534/genetics.110.121624. . ‘Control of germline torso expression by the BTB/POZ domain protein pipsqueak is required for embryonic terminal patterning in Drosophila.’ Genetics 187, No. 2: 513-521. doi:
- 10.1016/j.cub.2009.11.062. . ‘Sec24-Dependent Secretion Drives Cell-Autonomous Expansion of Tracheal Tubes in Drosophila.’ Current Biology 20, No. 1: 62-68. doi:
- 10.1016/j.cub.2010.09.069. . ‘Localization and activation of the drosophila protease easter require the ER-resident saposin-like protein seele.’ Current Biology 20, No. 21: 1953-1958. doi:
- 10.1242/jcs.052514. . ‘Kinase-activity-independent functions of atypical protein kinase C in Drosophila.’ Journal of Cell Science 122, No. 20: 3759-3771. doi:
- 10.1523/JNEUROSCI.5092-07.2008. . ‘Pumilio binds para mRNA and requires Nanos and Brat to regulate sodium current in drosophila motoneurons.’ Journal of Neuroscience 28, No. 9: 2099-2109. doi:
- 10.1371/journal.pone.0003241. . ‘γCOP is required for apical protein secretion and epithelial morphogenesis in Drosophila melanogaster.’ PLoS ONE 3, No. 9. doi:
- . . ‘Wollknauel is required for embryo patterning and encodes the Drosophila ALG5 UDP-glucose:dolichyl-phosphate glucosyltransferase.’ Development 135, No. 10: 1745-9ST - Wollknauel is required for embryo patterning and encodes the Drosophila ALG5 UDP-glucose:dolichyl-phosphate glucosyltransferase-.
- 10.1371/journal.pbio.0050145. . ‘Drosophila brakeless interacts with atrophin and is required for tailless-mediated transcriptional repression in early embryos.’ PLoS Biology 5, No. 6: 1298-1308. doi:
- 10.1073/pnas.0509260103. . ‘Genome-wide identification of mRNAs associated with the translational regulator PUMILIO in Drosophila melanogaster.’ Proceedings of the National Academy of Sciences of the United States of America 103, No. 12: 4487-4492. doi:
- 10.1016/j.cub.2005.11.072. . ‘serpentine and vermiform encode matrix proteins with chitin binding and deacetylation domains that limit tracheal tube length in Drosophila.’ Current Biology 16, No. 2: 186-194. doi:
- 10.1073/pnas.0506676102. . ‘Requirement for chitin biosynthesis in epithelial tube morphogenesis.’ Proceedings of the National Academy of Sciences of the United States of America 102, No. 47: 17014-17019. doi:
- 10.1016/j.mod.2004.05.006. . ‘Drosophila p24 homologues eclair and baiser are necessary for the activity of the maternally expressed Tkv receptor during early embryogenesis.’ Mechanisms of Development 121, No. 10: 1259-1273. doi:
- 10.1534/genetics.167.1.325. . ‘An F1 genetic screen for maternal-effect mutations affecting embryonic pattern formation in Drosophila melanogaster.’ Genetics 167, No. 1: 325-342. doi:
- 10.1016/S0925-4773(02)00410-0. . ‘Krapfen/dMyd88 is required for the establishment of dorsoventral pattern in the Drosophila embryo.’ Mechanisms of Development 120, No. 2: 219-226. doi:
- 10.1146/annurev.cellbio.19.031403.160043. . ‘Branching Morphogenesis of the Drosophila Tracheal System.’ Annual Reviews in Cell and Developmental Biology 2003: 623-647. doi:
- 10.1016/S1534-5807(02)00301-5. . ‘γ-tubulin37C and γ-tubulin ring complex protein 75 are essential for bicoid RNA localization during Drosophila oogenesis.’ Developmental Cell 3, No. 5: 685-696. doi:
- . ‘The Drosophila SHC adaptor protein is required for signaling by a subset of receptor tyrosine kinases.’ Molecular Cell 5, No. 2: 231-241.