Genetic analysis of cell specification in the Drosophila serotonergic lineage

This dissertation examines how a choice is made between a neuronal cell fate or an apoptotic cell fate during the development of the Drosophila serotonergic cell lineage. The serotonergic lineage of the Drosophila ventral nerve cord is a well characterized lineage that is derived from a neural stem cell called neuroblast 7-3 (NB7-3). NB7-3 produces six progeny that include two serotonin producing neurons, one motorneuron, one cell that expresses the insect neuropeptide corazonin, and two cells that undergo apoptosis.; In Chapter 1 we present evidence that during the development of the NB7-3 lineage Notch signaling specifies an apoptotic cell fate and the absence of Notch signaling specifies a neuronal cell fate. During asymmetric cell division the two serotonin producing neurons and the corazonin producing neuron receive a protein called Numb, which is an inhibitor of Notch signaling. The motorneuron and the two apoptotic cells do not receive Numb and maintain Notch signaling. Despite having active Notch signaling, the motorneuron does not undergo apoptosis. This implies that some factor other than Numb is necessary to prevent apoptosis of the motorneuron.; In Chapter 2 we present evidence that the motorneuron is protected from apoptosis by the transcription factor, Hunchback. We also show that ectopic expression of hunchback in the NB7-3 lineage can rescue the two cells which normally undergo Notch-induced apoptosis. In addition, ectopic expression of hunchback induces a conversion of the corazonin producing neuron into a serotonin producing neuron.; In Chapter 3 we further investigate the role of Notch signaling in the development of the NB7-3 lineage by examining mutant alleles of the Notch ligand, Delta, and the Notch effector, Suppressor of Hairless. We present evidence that Delta can activate Notch-induced apoptosis, but we also show that both Delta and Suppressor of Hairless have Notch-independent functions that are required during development of the serotonin neurons. We also examine several mutant alleles in the Wingless signaling pathway and demonstrate that mutations which reduce Wingless signaling decrease the number of detectable serotonin neurons. These results present a foundation for examining crosstalk between the Notch and Wingless signaling pathways during specification of the NB7-3 lineage.