Ziukaite, Ruta; (2019) Understanding the mechanisms behind BMP-mediated growth in Drosophila wing precursors. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The Bone Morphogenetic Protein 2/4 (BMP2/4)-like ligand Decapentaplegic (Dpp) is a morphogen that specifies positional information in Drosophila wing precursors. However, it has also been shown to play a vital role in regulating the growth of this tissue. The spatial and temporal requirements of Dpp for normal cell proliferation have been the subject of debate, which has intensified recently with the suggestion that the endogenous stripe of Dpp is not required for growth during the third larval instar. To address this claim and other questions pertaining to Dpp and growth, we have developed an HA- tagged conditional allele of dpp and a V5-tagged conditional allele of brk. These tools enable us to remove gene expression in a precise spatial and temporal manner with GAL4- driven expression of Flp recombinase. Contrary to a recent report, I show that deletion of the characteristic ‘stripe’ of dpp expression along the A/P compartment boundary is detrimental to wing disc growth. Furthermore, I find that continued dpp expression is essential throughout larval development for normal growth. I also show that graded levels of Dpp are not required to promote cell proliferation. Instead, I argue that Dpp has an indirect role in growth control and confirm that its primary function is to suppress brk expression in the medial regions of the wing disc. Overall, my results suggest that the endogenous stripe of dpp expression generates a gradient that specifies cell fates, but also promotes cell proliferation by ensuring that Dpp signalling stays above a certain threshold.

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