Harmansa, Stefan. Nanobodies as novel tools to study morphogen function "in vivo". 2016, PhD Thesis, University of Basel, Faculty of Science.
Restricted to Repository staff only until March 2017.
Available under License CC BY-NC-ND (Attribution-NonCommercial-NoDerivatives).
Official URL: http://edoc.unibas.ch/diss/DissB_11699
In the first part of this Thesis, I will discuss how SBNs allowed us to investigate the importance of the Dpp gradient on proliferation and growth control of the wing imaginal disc. Using morphotrap, a SBN that localizes to the outer cell surface, we could completely block gradient formation and study the effect of a loss of the Dpp gradient on patterning and growth. We find that induction of Dpp target genes, and hence patterning, directly depends on the spreading of Dpp. Furthermore, we show that the Dpp gradient is crucial for growth and size control of the medial wing disc region. Moreover, we find that the Dpp gradient is not necessary for proliferation and size control of the lateral region of the wing disc. This data challenges previously published growth models, in which growth control solely depends on the signaling
dynamics of Dpp.
In the second part of this Thesis I investigate the mechanism of Dpp gradient formation in the wing disc. The wing disc is a complex three-dimensional structure, consisting of two contiguous epithelial layers. How the long-range Dpp gradient is established in the wing disc remains controversial. I have created different SBNs that localize to specific subcellular regions along the apicobasal axis. These SBNs allow us to reduce or block the dispersal of specific gradient subfractions and assess their contribution to wing development. We find that EGFP::Dpp disperses along three main routes: within the epithelial plane of the wing disc, in the luminal cavity between the two epithelial layers and along the basal lamina. Preliminary results suggest that these subfractions encode for different functions of Dpp. While we find that the patterning function of Dpp is encoded by the basolateral subfractions, the growth function of Dpp seems to be influenced by all three subfraction. Further experiments will investigate how target cells perceive and integrate Dpp input from these different subfractions.
|Advisors:||Affolter, Markus and Basler, Konrad|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Affolter)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||1 Online-Ressource (120 Seiten)|
|Last Modified:||30 Aug 2016 09:47|
|Deposited On:||30 Aug 2016 09:46|
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