The Circadian Neuropeptide PDF has Sexually Dimorphic Effects on Activity Rhythms

Area of Science:

• Neuroscience
• Chronobiology
• Genetics

Background:

• The circadian system governs daily biological rhythms, with research often overlooking sex differences.
• Pigment Dispersing Factor (PDF) neurons are central to the Drosophila circadian network, synchronizing internal clocks.
• Mutations in Pdf or its receptor (PdfR) typically disrupt activity-rest cycles.

Purpose of the Study:

• To investigate sex-specific roles in Drosophila circadian rhythms.
• To determine the impact of PDF signaling pathway manipulation on male and female behavior.
• To explore the influence of specific clock neuron groups (M-cells) on circadian timing.

Main Methods:

• Utilized CRISPR-Cas9 gene editing to mutate Pdf in specific neurons (LNvs).
• Assessed activity-rest cycles under constant conditions in wild-type and mutant Drosophila strains.
• Manipulated molecular clock speed in M-cells to observe behavioral effects.

Main Results:

• Female flies showed less disruption of circadian rhythms compared to males when Pdf or PdfR was mutated.
• CRISPR-Cas9 mutagenesis of Pdf in LNvs had a greater impact on male rhythmic behavior.
• Altering clock speed in M-cells produced sexually dimorphic behavioral phenotypes, more pronounced in males.

Conclusions:

• The female circadian system demonstrates greater resilience to disruptions in the PDF signaling pathway.
• Circadian timekeeping appears more distributed across the neural network in females compared to males.
• Sex is a critical variable influencing the architecture and function of the circadian clock network.