Motor neuron development in the Drosophila embryonic central nervous system

The central nervous system (CNS) is a critical organ that receives and processes stimuli to generate a response. Multiple neuronal classes are required to carry out these tasks. Due to the number of disorders resulting from improper CNS development, it is important to understand the developmental mechanisms that generate distinct neuronal classes. This study focuses on understanding motor neuron development in the fruit fly Drosophila melanogaster by characterizing the role of candidate genes, investigating the regulation of neuromuscular junction (NMJ) components, and identifying novel genes via a nonbiased genetic screen.;Analysis of the candidate genes Zfh1 and Nkx6 reveal that motor neuron characteristics are genetically separated. Functional studies show that both genes regulate ISNb motor axon CNS exit but not overall motor neuron fate. Previously, the transcription factor Eve was also shown to regulate CNS exit for ISN motor neurons. Together these data suggest that motor axon CNS exit, and perhaps motor neuron identity, is regulated by distinct pathways in each class of motor neurons.;The NMJ pathway requires BMP signaling. BMP ligands signal through a heterodimeric receptor complex to activate the transcription factor Mad. The receptors and mad are each expressed in distinct temporal and spatial patterns indicating independent regulation. This is consistent with the model that motor neuron characteristics are independently regulated, rather than relying on a single motor neuron pathway for proper development.;I employed a nonbiased genetic strategy to identify novel genes that regulate motor axon CNS exit. Deficiency screening identified mutant phenotypes ranging from CNS exit failure of one or multiple motor neuron classes to extra axons exiting the CNS, however, no deficiency causes a failure of all motor axons to undergo CNS exit. This indirectly supports the conclusion that motor neuron classes are generated by independent genetic pathways. The data from this work supports an emerging model that motor neuron specification is determined by the accumulation of multiple characteristics in the same cell, rather than a single pathway regulating the motor neuron characteristics.