Document Type
Article
Publication Date
1-1-2023
Original Citation
Schirmer A,
Kumar V,
Schook A,
Song E,
Marshall M,
Takahashi J.
Cry1 expression during postnatal development is critical for the establishment of normal circadian period Front Neurosci. 2023;17:1166137.
Keywords
JMG, cryptochrome, circadian rhythms, period length, development, gene expression
JAX Source
Front Neurosci. 2023;17:1166137.
ISSN
1662-4548
PMID
37389366
DOI
https://doi.org/10.3389/fnins.2023.1166137
Grant
This work was supported by a Silvio O. Conte Center NIH Grant P50 MH074924 to JST. JST is an Investigator in the Howard Hughes Medical Institute.
Abstract
The mammalian circadian system generates an approximate 24-h rhythm through a complex autoregulatory feedback loop. Four genes, Period1 (Per1), Period2 (Per2), Cryptochrome1 (Cry1), and Cryptochrome2 (Cry2), regulate the negative feedback within this loop. Although these proteins have distinct roles within the core circadian mechanism, their individual functions are poorly understood. Here, we used a tetracycline trans-activator system (tTA) to examine the role of transcriptional oscillations in Cry1 and Cry2 in the persistence of circadian activity rhythms. We demonstrate that rhythmic Cry1 expression is an important regulator of circadian period. We then define a critical period from birth to postnatal day 45 (PN45) where the level of Cry1 expression is critical for setting the endogenous free running period in the adult animal. Moreover, we show that, although rhythmic Cry1 expression is important, in animals with disrupted circadian rhythms overexpression of Cry1 is sufficient to restore normal behavioral periodicity. These findings provide new insights into the roles of the Cryptochrome proteins in circadian rhythmicity and further our understanding of the mammalian circadian clock.
Comments
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.