M.phil Thesis Summary

Retrograde signals are diffusible, secreted, or membrane bound factors that transmit information from the post- to presynaptic membranes of a synapse. They have long been recognised as important factors in determining the development of neural networks. On receiving a retrograde signal, a neuron`s pre- and postsynaptic neurites can undergo morphological or physiological changes.

In this thesis I have used the accessible and well-characterised locomotor system of the Drosophila third instar larva to investigate retrograde signalling between the dorsal anterior 1 (DA1) muscle and anterior corner cell motoneurons (aCC MNs). Previous studies with Drosophila demonstrate that muscle-derived retrograde signals are involved in the growth and homeostasis of the neuromuscular junction. In this project I have focused on the central changes that occur in the dendritic arbor of the motoneuron.

For my experiments I bred a stock of flies that expressed Gal4 in the DA1 muscles and LexA in the aCC-MNs. Therefore using the UAS-mCD8-GFP and LexAop-myr::cherry reporters ensured that the muscles fluoresced green and the MNs red. This genotype allowed me to target the expression of genes to the DA1 muscles. In this way I could express transgenes that alter muscle size (UAS-myrPi3K and UAS-Cyclin E), and then observe the corresponding changes in the MN dendrites.

As a muscle grows its synaptic resistance decreases, meaning that a larger current is required to depolarize the cell. The hypothesis behind this project was that retrograde signals could induce a longer dendritic arbor when innervating a muscle that is hypertrophied (vice versa for smaller muscles). This is based on the fact that longer arbors receive more presynaptic stimulation from interneurons, and this results in longer bursts of action potentials along the MN axon. Therefore a longer arbor restores physiologically appropriate levels of muscle depolarisation in larger muscles.

The results of this thesis suggest that the size of the DA1 muscle determines the length of the contralateral arbor in the aCC motoneuron. This is a localised effect as the ipsilateral arbor does not appear to be affected.

This project therefore supports the hypothesis that muscle-derived retrograde signals can regulate the dendritic complexity of a motoneurons in third instar Drosophila larvae.