For animals to walk properly, motor neurons (MNs) need to reach their target muscles in the leg and they need to arborize properly. Cell adhesion molecules (CAMs) have pivotal roles in a variety of neural development processes including arborization. Two Immunoglobulin Super Family (IgSF) CAMs, DIP-α and its interacting partner Dpr10, have been shown to play key roles in leg MN arborization in flies. DIP-α is expressed by three leg MNs and dpr10 is expressed by leg muscles. When either DIP-α or dpr10 are removed in flies MNs reach their target but fail to arborize their branches. Interestingly, DIP-α and Dpr10 have some of the highest binding affinities relative to other DIPs and Dpr interacting pairs. Therefore, in this thesis I ask how important are these relatively high affinities and do the MNs have different affinity requirements?
I show that decreasing and increasing the affinity between these two proteins in vivo has adverse effects on MN arborization and that different MNs rely on different thresholds of DIP-α::dpr10 binding affinities to arborize properly. Based on these experiments, I then ask how DIPs and Dprs interact when they are co-expressed by the same neuron. Here I provide evidence that altering the ratio of DIP-a::dpr10::dpr6 can inhibit DIP-α’s ability to bind in trans with Dpr10.
Furthermore, together with Dr. Nick Morano in the Shapiro lab, we show that DIP-α has a longer linker domain compared to DIPs that are not able to bind in cis and that removing this linker domain in vivo phenocopies some of the effects seen by removing co-expressed dpr6 or dpr10 in DIP-α MNs. Therefore, although DIP-α and its partners Dpr6 and Dpr10 are expressed in MNs, relative concentrations and cis interactions in MNs dictate how DIP-α interacts in trans with Dpr10.
Together, this thesis provides a better understanding as to how interactions between CAMs can be modified via affinities, concentration, and co-expression in vivo to ultimately shape axon morphology of Drosophila leg MNs.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/ajad-ky40 |
| Date | January 2024 |
| Creators | Lopez, Davys |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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