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Dimorphic differentiation of female-specific neuronal populations and behavior in Drosophila

University of British Columbia

Over the past years, numerous studies have advanced our understanding of the generation and function of the sex-specific neuronal populations that control sex-specific behaviours. Prior to the work presented in this thesis, no female-specific subsets of neurons had been identified in Drosophila; thus, all models and studies of sex-specific neurons have had a male bias. This thesis describes the first identification and characterization of a female-specific neuronal population in the central nervous system of Drosophila, the Ilp7-motoneurons. These neurons innervate the oviduct and are required for egg-laying. We further identified cellular and genetic mechanisms that direct the dimorphic generation of these female-specific neurons. Programmed cell death of post-mitotic nascent Ilp7-motoneurons in males accounts for their female-specific generation in a process regulated by a non-canonical and dosage-sensitive pro-apoptotic role for the male fruitless isoform (fruM). Thus, we find that analysis of female-specific neuron generation unveils novel mechanisms of dimorphic nervous system construction. Our characterization of Ilp7-motoneurons led to a collaboration with Eric Lai (Sloan Kettering, USA), to study the neuronal basis of the female sterility phenotype of the ∆mir mutant, a deficiency in the bidirectional mir-iab-4 and mir-iab-8 miRNA locus of the Bithorax-Complex. We find that female sterility arises from derepression of mir-iab-4/8 targets, Ultrabithorax and homothorax, in fru-expressing neuronal populations of the posterior abdominal segments of the ventral nerve cord. This results in numerous phenotypes that each likely contribute to sterility. ∆mir females have reduced Ilp7-motor innervation of the oviduct. ∆mir virgin females are constitutively unreceptive to males; however, if mated, they fail to increase egg production. Our data suggests a novel mechanism that may explain this phenotype; after mating, sex peptide from the male seminal fluid is retained in the female reproductive tract, rather than being transferred to the hemolymph, where it is believed to effect the increase in egg production. Ongoing work aims to identify the neuronal populations that are disrupted in ∆mir mutants. Taken together, this thesis provides novel insight and models to further our understanding of female-specific neuronal differentiation, a field that has long been under-represented in the literature.

Text

2018-10-31

Attribution-NonCommercial-NoDerivs 2.5 Canada

http://hdl.handle.net/2429/50821

Cell and Developmental Biology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/2.5/ca/