| The primary focus of this thesis has been to examine distal-less function(s) during the development of the larval olfactory system in Drosophila melanogaster. distal-less encodes a homeodomain transcription factor that is expressed in developing appendages in organisms throughout metazoan phylogeny. However, based on observations of distal-less expression in the limbless nematode Caenorhabditis elegans and the primitive chordate amphioxus, it was proposed that the ancestral function of distal-less was in the nervous system. Consistent with this hypothesis, the vertebrate homologs of dll, the Dlx genes, play critical roles in brain development. Although distal-less expression in the invertebrate nervous system has been reported, its function(s) there have not been investigated. I present here the first account of distal-less function in the invertebrate nervous system and establish that distal-less is necessary for the specification and morphological development of larval olfactory neurons in Drosophila melanogaster. distal-less continues to be expressed in chemosensory organs during larval stages, and behavioral assays indicate distal-less also functions in postmitotic neurons to mediate larval olfactory behavior. The findings presented here provide support for a fundamental role for distal-less in invertebrate neural development and neural function. The manipulations and techniques available in Drosophila make it a powerful model system for the identification of genetic relationships and functions that are, due to issues such as redundancy, difficult to discern in a vertebrate model system. Studies of Drosophila distal-less have the potential to impact human health in at least two ways. First, insects and other arthropods are responsible for the spread of diseases such as malaria, West Nile and Lyme disease. Olfactory cues are used as a means of locating human hosts, and therefore, a greater understanding of arthropod olfaction can aid in the development of novel strategies for combating the transmission of such diseases. Second, the Dlx genes have been implicated in a number of developmental neuropathologies including autism, Down syndrome, Rhett syndrome and epilepsy. Comparative studies of dll/Dlx functions in the invertebrate and vertebrate nervous systems can provide insight into how disruptions in Dlx function result in aberrant neural development and the etiology of these disorders. |
