AUTHOR=Schirmer Aaron E. , Kumar Vivek , Schook Andrew , Song Eun Joo , Marshall Michael S. , Takahashi Joseph S. 

TITLE=Cry1 expression during postnatal development is critical for the establishment of normal circadian period

JOURNAL=Frontiers in Neuroscience

VOLUME=17

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1166137

DOI=10.3389/fnins.2023.1166137

ISSN=1662-453X

ABSTRACT=<p>The mammalian circadian system generates an approximate 24-h rhythm through a complex autoregulatory feedback loop. Four genes, <italic>Period1</italic> (<italic>Per1</italic>), <italic>Period2</italic> (<italic>Per2</italic>), <italic>Cryptochrome1</italic> (<italic>Cry1</italic>), and <italic>Cryptochrome2</italic> (<italic>Cry2</italic>), 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 <italic>Cry1</italic> and <italic>Cry2</italic> in the persistence of circadian activity rhythms. We demonstrate that rhythmic <italic>Cry1</italic> 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 <italic>Cry1</italic> expression is critical for setting the endogenous free running period in the adult animal. Moreover, we show that, although rhythmic <italic>Cry1</italic> expression is important, in animals with disrupted circadian rhythms overexpression of <italic>Cry1</italic> 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.</p>