Dendritic Disasters: Investigating the Role of Muscleblind (mbl) in Drosophila class IV Dendritic Arborization Neurons

Abstract

The ability of an organism to respond to its environment relies on effective signal transduction in neurons of the peripheral nervous system (PNS). As a result, the organization the dendritic arbor in multidendritic PNS neurons must be tightly regulated. Our lab has shown that the Drosophila melanogaster RNA-binding protein, Muscleblind (Mbl) is important for the formation of the dendritic arbor, in class IV dendritic arborization (da) neurons – multidendritic neurons of the Drosophila PNS that function in nociception. This thesis seeks to further understand the morphological defects associated with mbl knockdown, identify the molecular and cytoskeletal disruptions caused by Mbl reduction, observe the impact that these defects have on larval nociception and propose a model of Mbl function. Ultimately, I find that mbl knockdown causes an increase in terminal branch density and a decrease in field coverage – the ability for the dendritic arbor to cover the epidermal space. However, the percentage of the arbor that invaginates into the epidermis, a process termed enclosure, remains unchanged between the wild-type and mbl RNAi class IV da neurons. In terms of cytoskeletal organization, mbl RNAi class IV da neurons show a decrease in stable microtubules. Overall, these defects result in larval hypersensitivity to global thermal stimulus but no impact on mechanical nociception. It is our hope that these data can be used to better understand the role of Mbl, and its human homolog muscle-blind like protein (MBNL) in regulating mRNA stability and preventing disorders like Myotonic Dystrophy (MD), a genetic condition in humans mutant for MBNL.