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.
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.
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).
Januschke, J. and Wodarz, A. (2017) Notch Signaling: "Where Is the Action?" Current biology : CB. 27, R760-R762
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
Pampalona, J., Januschke, J., et al. (2015). "Time-lapse recording of centrosomes and other organelles in Drosophila neuroblasts." Methods Cell Biol 129: 301-315.
Januschke, J. and Nathke, I. (2014). "Stem cell decisions: a twist of fate or a niche market?" Semin Cell Dev Biol 34: 116-123.
Januschke, J., Reina, J., et al. (2013). "Centrobin controls mother-daughter centriole asymmetry in Drosophila neuroblasts." Nat Cell Biol 15(3): 241-248.
Januschke, J., Llamazares, S., et al. (2011). "Drosophila neuroblasts retain the daughter centrosome." Nat Commun 2: 243.
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.
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.