The Drosophila gene turtle regulates class specific dendrite morphogenesis and larval locomotion

As the primary site for synaptic input and signal integration, neuronal dendrites perform a fundamental role in all functions of the nervous system including sensory perception, motor control, and learning and memory. Molecular insight into the mechanisms mediating dendrite morphogenesis is key for advancing our knowledge of these remarkable structures as well as for understanding the pathologies of nervous system diseases and aging. As the shape of a neuron's dendrites largely determines its function, studies of dendrite morphogenesis are critical for understanding neural circuit assembly and more globally nervous system activity. To elucidate the molecular bases underlying dendrite development, the dendritic arborization (da) neurons of the Drosophila melanogaster peripheral nervous system were used as a model system.;This thesis presents evidence that the conserved immunoglobulin superfamily (IgSF) member turtle (tutl) is required for class specific dendritic morphogenesis. Immunohistochemistry analyses revealed punctate expression of Tutl protein in da neuron cell bodies and dendrites. Loss-of-function experiments revealed that in morphologically complex neurons, tutl is required for promoting proper dendritic elaboration and receptive field coverage via effects on overall dendritic growth, whereas in morphologically simpler neurons, tutl primarily effects dendritic branching. In contrast to the tutl LOF analyses, overexpression of tutl in each class of da neuron did not produce any significant phenotypic changes. The homeodomain transcription factor Cut was shown to positively regulate tutl expression in da neurons. Finally, behavioral analyses indicate tutl is required for mediating normal larval locomotion.;Collectively, these studies reveal tutl as a novel regulator of class specific dendrite morphogenesis. The class-specific functions of tutl provide important information about the different molecular processes at work in various neuron subtypes. The regulatory interaction between cut and tutl represent the beginnings of understanding a new pathway regulating the acquisition of class-specific neuronal characteristics. Moreover, given the functional conservation between Drosophila and vertebrates for genes such as turtle and cut , (Shi et al., 2004a; Lemieux et al., 1994; Grueber et al., 2003), these studies may provide intriguing entry points for extending the findings obtained in Drosophila via model system studies in vertebrates.