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Knapp, E. M.

Publications and source records attributed to Knapp, E. M..

3 recordsLinked to original sources

Drosophila cells that express octopamine receptors can either inhibit or promote oviposition

Adrenergic signaling is known to play a critical role in regulating female reproductive processes in both mammals and insects. In Drosophila, the ortholog of noradrenaline, octopamine (Oa), is required for ovulation as well as several other female reproductive processes. Loss of function studies using mutant alleles of receptors, transporters, and biosynthetic enzymes for Oa have led to a model in which disruption of octopaminergic pathways reduces egg laying. However, neither the complete expression pattern in the reproductive tract nor the role of most octopamine receptors in oviposition is known. We show that all six known Oa receptors are expressed in peripheral neurons at multiple sites within in the female fly reproductive tract as well as in non-neuronal cells within the sperm storage organs. The complex pattern of Oa receptor expression in the reproductive tract suggests the potential for influencing multiple regulatory pathways, including those known to inhibit egg-laying in unmated flies. Indeed, activation of some neurons that express Oa receptors inhibits oviposition, and neurons that express different subtypes of Oa receptor can affect different stages of egg laying. Stimulation of some Oa receptor expressing neurons (OaRNs) also induces contractions in lateral oviduct muscle and activation of non-neuronal cells in the sperm storage organs by Oa generates OAMB-dependent intracellular calcium release. Our results are consistent with a model in which adrenergic pathways play a variety of complex roles in the fly reproductive tract that includes both the stimulation and inhibition of oviposition.

neuroscience↗

The bHLH-PAS transcriptional complex Sim:Tgo plays active roles in late oogenesis to promote follicle maturation and ovulation

Across species, ovulation is a process induced by a myriad of signaling cascades that ultimately results in activation of proteolytic enzymes and degradation of the follicle wall to release encapsulated oocytes. Follicles need to first mature and gain ovulatory competency before ovulation. However, the signaling pathways regulating follicle maturation are incompletely understood in Drosophila and other species. Our previous work showed that bHLH-PAS transcription factor Single-minded (Sim) likely plays important roles for follicle maturation downstream of the NR5A-family nuclear receptor Ftz-f1 in Drosophila. Here, we explore the mechanism of Sim-regulated follicle maturation. We demonstrate that Tango (Tgo), another bHLH-PAS protein acts as a cofactor of Sim to promote follicle cell differentiation from stages 10 to 12. In addition, we discovered that re-upregulation of Sim in stage-14 follicle cells is also essential to promote ovulatory competency by upregulating octopamine receptor in mushroom body (OAMB), matrix metalloproteinase 2 (Mmp2), and NADPH oxidase (NOX), either independent of or in conjunction with the zinc-finger protein Hindsight (Hnt). All of these factors are critical for successful ovulation. Together, our work indicates that the transcriptional complex Sim:Tgo plays multiple roles in late-stage follicle cells to promote follicle maturation and ovulation.

developmental biology↗

Mutation of the Drosophila serotonin transporter dSERT disrupts courtship and feeding and increases both daytime and nighttime sleep

The Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. The mechanisms by which inhibition of SERT activity influences behavior are poorly understood. To address this question in the model organism Drosophila melanogaster, we developed new loss of function mutations in Drosophila SERT (dSERT). Previous studies in both flies and mammals have implicated serotonin as an important neuromodulator of sleep, and our newly generated dSERT mutants show an increase in total sleep and altered sleep architecture. Differences in daytime vs. nighttime sleep architecture as well as genetic rescue experiments unexpectedly suggest that distinct serotonergic circuits may modulate daytime versus nighttime sleep. dSERT mutants also show defects in copulation and food intake, akin to the clinical side effects of SSRIs. Starvation did not overcome the sleep drive in the mutants. Additionally in males, but not female dSERT mutants, the drive to mate also failed to overcome sleep drive. dSERT may be used to further explore the mechanisms by which serotonin regulates sleep and its interplay with other complex behaviors. Author SummaryMany medications used to treat depression and anxiety act by changing serotonin levels in the brain. Fruit flies also use serotonin and can be used as a model to study the brain. We have made a fly mutant for the serotonin transporter (SERT), which is the target of antidepressants in humans. The mutants sleep more, eat less, and have a decreased sex drive. These flies can be used to study the neuronal pathways by which serotonin regulates sleep, eating and sexual behaviors and may help us to understand the behavioral effects of antidepressants.

neuroscience↗