Dr Jens Januschke
Establishment of cell polarity in rapidly dividing Drosophila stem cells
The ability to generate different cell types is a fundamental feature of multicellular life forms. Asymmetric cell division (ACD) is an important process that helps to produce the repertoire of cell types. ACD is particularly important for the function of stem cells as it provides the bases for self-renewing fate generating divisions during development as well as for tissue homeostasis in the adult. Faulty stem cell division has dramatic consequences for the integrity of organisms as it can compromise normal initiation and maintenance of tissues. We are interested in the dynamics of ACD in stem cells. A long-term goal is to understand how cycling stem cells robustly control ACD to prevent errors in cell fate generation.
We use Drosophila neural stem cells of the developing central nervous system called, neuroblasts, to study this process. Neuroblasts are highly proliferative and provide a well-characterised model system for ACD. As in many other stem cells, ACD in neuroblasts relies on the establishment of a polarity axis that governs the orientation of the mitotic spindle to transmit cell fate information differentially to the resulting daughter cells upon cytokinesis (see Video 1). However, progression through the cell cycle is accompanied by dramatic subcellular rearrangements (Video 1), raising the question of how continuity of cell polarity is ensured from one cell cycle to the next.
Imaging living neuroblasts in primary cell culture as well as in whole mount explants of the developing brain, we document and measure the dynamics of cell polarisation during consecutive neuroblast cycles. We focus particularly on the subcellular localisation of mRNA’s to determine their contribution to the establishment of cell polarity and cell fate specification.
Popow, O., Paulo, JA., Tatham, M.,Volk, M., Rojas-Fernandez, A., Loyer, N., Newton, I., Januschke, J., Haigis, KM & Nathke, I. (2019) Identification of Endogenous Adenomatous Polyposis Coli Interaction Parners and β-Catenin-Independent Targets by Proteomics. Molecular Cancer Research. doi/10.1158/1541-7786.MCR-18-1154 PMID 31160382 Read Article
Loyer, N., Januschke, J (2019) Where does asymmetry come from? Illustrating principles of polarity and asymmetry establishment in Drosophila neuroblasts. doi/10.1016/j.ceb.2019.07.018 PMID 31698250 Read Article
Hannford, M.R., Loyer, N., Tonelli, F., Zoltner, M. and Januschke, J. (2019) A chemical-genetics approach to study the role of atypical Protein Kinase C in Drosophila. Development 146, dev170589. doi/10.1242/dev.170589 PMCID 6361133 PMID 30635282 Read Article
Hannaford, M.R., Ramat, A., Loyer, N., Januschke, J. (2018) aPKC-mediated displacement and actomyosin-mediated retention polarize Miranda in Drosophila neuroblasts. eLife. 7:1-22. doi/10.7554/eLife.29939.001 PMCID 5783611 PMID 29364113 Read Article
Clemente, G.D., Hannaford, M.R., Beati, H., Kapp, K., Januschke, J., Griffis, E.R., Müller, H.A.J. (2018) Requirement of the Dynein-Adaptor Spindly for Mitotic and Post-Mititotic Functions in Drosophila. Journal of Developmental Biology. 6(2). doi/10.3390/jdb6020009 PMCID 6027351 PMID 29615558 Read Article
Loyer, N. Januschke, J. (2018) The last-born daughter cell contributes to division orientation of Drosophila larval neuroblasts. Nature Comm 9:3745. doi/10.1038/S41467-018-06276-0 PMCID 6138640 PMID 30218051 Read Article
Januschke, J. and Wodarz, A. (2017) Notch Signaling: Where Is the Action? Current biology: CB. 27, R760-R762. doi.org/10.1016/j.cub.2017.06.072 PMID 28787607 Read Article
Ramat, A., Hannaford, M. and Januschke, J. (2017) Maintenance of Miranda Localization in Drosophila Neuroblasts Involves Interaction with the Cognate mRNA. Current Biology: CB. 27, 2101-2111 e2105. doi/10.1016/j.cub.2017.06.016 PMCID 5526833 PMID 28690114 Read Article
Pampalona, J., Januschke, J., et al. (2015). Time-lapse recording of centrosomes and other organelles in Drosophila neuroblasts. Methods Cell Biol 129: 301-315. doi/10.1016/bs.mcb.2015.03.003 PMID 26175445 Read Article
Januschke, J. and Nathke, I. (2014). Stem cell decisions: a twist of fate or a niche market? Seminars in Cell Dev Biol 34: 116-123. doi/10.1016/j.semcdb.2014.02.014 PMCID 4169664 PMID 24613913 Read Article
Januschke, J., Reina, J., et al. (2013) Centrobin controls mother-daughter centriole asymmetry in Drosophila neuroblasts. Nat Cell Biol 15(3): 241-248. doi/10.1038/ncb2671 PMID 23354166 Read Article
Januschke, J., Llamazares, S., et al. (2011) Drosophila neuroblasts retain the daughter centrosome. Nat Commun 2: 243. doi/10.1038/ncomms1245 PMCID 3072095 PMID 21407209 Read Article
Wang, C., Li, S., Januschke, J., et al. (2011) An ana2/ctp/mud complex regulates spindle orientation in Drosophila neuroblasts. Dev Cell 21(3): 520-533. doi/10.1016/j.devcel.2011.08.002 PMID 21920316 Read Article
Januschke, J. and Gonzalez, C. (2010) The interphase microtubule aster is a determinant of asymmetric division orientation in Drosophila neuroblasts. J Cell Biol 188(5): 693-706. doi/10.1083/jcb.200905024 PMID 20194641 . Read Article