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. 2023 Nov 28;4(1):zpad045.
doi: 10.1093/sleepadvances/zpad045. eCollection 2023.

A conserved role for frizzled in sleep architecture

Nicholas R Gessner  1 , Morteza Peiravi  2 , Fan Zhang  3 , Shemsiya Yimam  1 , Danielle Springer  2 , Susan T Harbison  1
Affiliations

A conserved role for frizzled in sleep architecture

Nicholas R Gessner et al. Sleep Adv. .

Abstract

Previous studies of natural variants in Drosophila melanogaster implicated the Wnt signaling receptor frizzled in sleep. Given that the Wnt signaling pathway is highly conserved across species, we hypothesized that frizzled class receptor 1 (Fzd1), the murine homolog of frizzled, would also have a role in sleep. Using a CRISPR transgenic approach, we removed most of the Fzd1 coding region from C57BL/6N mice. We used a video assay to measure sleep characteristics in Fzd1-deficient mice. As Wnt signaling is known to affect visuospatial memory, we also examined the impact of the deletion on learning and memory using the novel object recognition (NOR) paradigm. Fzd1-deficient mice had altered sleep compared to littermate controls. The mice did not respond differently to the NOR paradigm compared to controls but did display anxiety-like behavior. Our strategy demonstrates that the study of natural variation in Drosophila sleep translates into candidate genes for sleep in vertebrate species such as the mouse.

Keywords: Drosophila melanogaster; Wnt signaling pathway; mus musculus; novel object recognition test; open-field test; sleep.

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Figures

Figure 1.
Figure 1.
NOR task schema. Figure created with BioRender.com.
Figure 2.
Figure 2.
Sleep phenotypes of Fzd1 knockout mice. (A) Day bout number, (B) Night bout number, (C) 24-hour bout number, (D) Day avg. bout length (min.), (E) Night avg. bout length (min.), (F) 24-hour avg. bout length (min.), (G) Day sleep duration (min.), (H) Night sleep duration (min.), and (I.) 24-hour sleep duration (min.). Data are plotted as box and whisker plots with median, 10th and 90th percentile values. Circles indicate data for individual animals. * denotes significant differences via post hoc Tukey test.
Figure 3.
Figure 3.
Select NOR task results. (A) Recognition Index scores, (B) Edge time, and (C) Immobile time in the NOR task for Fzd1+/+, Fzd1+/−, and Fzd1+/− mice. Data are plotted as box and whisker plots with median, 10th and 90th percentile values. Circles indicate data for individual animals. The horizontal benchmark line in (A) represents chance discrimination index (50%), and the asterisk indicates genotypes significant from 50%. * denotes significant difference via post hoc Tukey test in (B) and (C).
See this image and copyright information in PMC

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