Characterization of mWake expression in the murine brain.

Autor: Bell BJ; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA., Wang AA; Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA., Kim DW; Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland, USA., Xiong J; Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University, Baltimore, Maryland, USA., Blackshaw S; Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland, USA., Wu MN; Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland, USA.
Jazyk: angličtina
Zdroj: The Journal of comparative neurology [J Comp Neurol] 2021 Jun; Vol. 529 (8), pp. 1954-1987. Date of Electronic Publication: 2020 Nov 10.
DOI: 10.1002/cne.25066
Abstrakt: Structure-function analyses of the mammalian brain have historically relied on anatomically-based approaches. In these investigations, physical, chemical, or electrolytic lesions of anatomical structures are applied, and the resulting behavioral or physiological responses assayed. An alternative approach is to focus on the expression pattern of a molecule whose function has been characterized and then use genetic intersectional methods to optogenetically or chemogenetically manipulate distinct circuits. We previously identified WIDE AWAKE (WAKE) in Drosophila, a clock output molecule that mediates the temporal regulation of sleep onset and sleep maintenance. More recently, we have studied the mouse homolog, mWAKE/ANKFN1, and our data suggest that its basic role in the circadian regulation of arousal is conserved. Here, we perform a systematic analysis of the expression pattern of mWake mRNA, protein, and cells throughout the adult mouse brain. We find that mWAKE labels neurons in a restricted, but distributed manner, in multiple regions of the hypothalamus (including the suprachiasmatic nucleus, dorsomedial hypothalamus, and tuberomammillary nucleus region), the limbic system, sensory processing nuclei, and additional specific brainstem, subcortical, and cortical areas. Interestingly, mWAKE is also observed in non-neuronal ependymal cells. In addition, to describe the molecular identities and clustering of mWake + cells, we provide detailed analyses of single cell RNA sequencing data from the hypothalamus, a region with particularly significant mWAKE expression. These findings lay the groundwork for future studies into the potential role of mWAKE + cells in the rhythmic control of diverse behaviors and physiological processes.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE