Characterization of mWake expression in the murine brain

Area of Science:

• Neuroscience
• Chronobiology
• Molecular Biology

Background:

• Mammalian brain structure-function studies often use lesion-based methods.
• An alternative approach involves studying gene expression patterns to identify and manipulate neural circuits.
• WIDE AWAKE (WAKE) is a Drosophila clock output molecule regulating sleep.

Purpose of the Study:

• To systematically analyze the expression pattern of the mouse homolog of WAKE (mWAKE/ANKFN1) in the adult mouse brain.
• To identify the specific cell types and brain regions expressing mWAKE.
• To lay the groundwork for future research on mWAKE's role in circadian rhythms and behavior.

Main Methods:

• Analysis of mWAKE mRNA, protein, and cell expression throughout the adult mouse brain.
• Utilizing single-cell RNA sequencing data, particularly from the hypothalamus.
• Mapping mWAKE expression in neuronal and non-neuronal cells.

Main Results:

• mWAKE mRNA, protein, and cells are expressed in a restricted but distributed pattern across multiple brain regions.
• Key areas include the hypothalamus (SCN, DMH, TMR), limbic system, sensory nuclei, brainstem, subcortical, and cortical regions.
• mWAKE is also found in non-neuronal ependymal cells, and single-cell RNA sequencing provides molecular insights into mWAKE+ cells in the hypothalamus.

Conclusions:

• The expression pattern of mWAKE is widespread yet specific across the adult mouse brain.
• mWAKE+ cells are found in diverse neuronal populations and ependymal cells.
• These findings are crucial for future investigations into mWAKE's function in regulating arousal, sleep, and other circadian-controlled processes.