Dissecting the cell biology of the stem cell niche in the Drosophila testis and the underlying signal transduction cascades
Final Report Abstract
During the course of the project I have addressed all topics proposed both in the initial application and for the extension for the second funding period. In particular, we have improved our understanding of niche function, following up on our DamID experiments with transcriptome studies of purified cell populations in the testis. We could thus support our initial model of “stem cell micromanagment”, whereby the niche signals directly impinge on individual stem cell behaviours rather than specifying a global stem cell fate in a binary cell fate decision. We could link the metabolic differences identified by our transcriptome studies to regulation of stem cell proliferation, and demonstrate that the apparent combinatorial regulation of stem cell fate by multiple niche signals is an artefact of NFkB-mediated cell competition specifically in the stem cells. In parallel, using the reporter technology developed in my lab helped us to generate insight in the cell biological implementation of the Hh signalling cascade, one of the most enigmatic pathways present in most metazoa . Finally, we combined cell biological, biochemical and biophysical techniques to dissect the role of endocytosis for cytokine receptor signalling, which differs markedly from the simple signal downregulation of the signals seen in many other pathways.
Publications
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US patent 8771682 , Methods and Compositions for Reducing Interleukin-4 or Interleukin-13 Signaling
Christian Bökel
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Generation and interpretation of FGF morphogen gradients in vertebrates. Current Opinion in Genetics & Development, 23(4), 415-422.
Bökel, Christian & Brand, Michael
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Phosphorylation of the Smo tail is controlled by membrane localization and is dispensable for clustering. Journal of Cell Science.
Kupinski, Adam P.; Raabe, Isabel; Michel, Marcus; Ail, Divya; Brusch, Lutz; Weidemann, Thomas & Bökel, Christian
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Dynamics and Interaction of Interleukin-4 Receptor Subunits in Living Cells. Biophysical Journal, 107(11), 2515-2527.
Gandhi, Hetvi; Worch, Remigiusz; Kurgonaite, Kristina; Hintersteiner, Martin; Schwille, Petra; Bökel, Christian & Weidemann, Thomas
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Endocytosis and Signaling during Development. Cold Spring Harbor Perspectives in Biology, 6(3), a017020-a017020.
Bokel, C. & Brand, M.
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A cell based, high throughput assay for quantitative analysis of Hedgehog pathway activation using a Smoothened activation sensor. Scientific Reports, 7(1).
Albert, Evgenii A. & Bökel, Christian
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Direct control of somatic stem cell proliferation factors by the Drosophila testis stem cell niche. Development, 145(17).
Albert, Eugene A.; Puretskaia, Olga A.; Terekhanova, Nadezhda V.; Labudina, Anastasia & Bökel, Christian
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Innate immune signalling drives loser cell elimination during stem cell competition in theDrosophilatestis. Cold Spring Harbor Laboratory.
Hof-Michel, Silvana; Cigoja, Ljubinka; Huhn, Sabina & Bökel, Christian
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Transcriptome analysis of somatic cell populations in theDrosophilatestis links metabolism and stemness. Cold Spring Harbor Laboratory.
Hof-Michel, Silvana & Bökel, Christian
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Cell-cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis. Cell Reports, 39(6), 110774.
Sainz de la Maza, Diego; Hof-Michel, Silvana; Phillimore, Lee; Bökel, Christian & Amoyel, Marc
