Cry1 expression during postnatal development is critical for the establishment of normal circadian period
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1166137/full |
| _version_ | 1797804509267755008 |
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| author | Aaron E. Schirmer Aaron E. Schirmer Vivek Kumar Vivek Kumar Andrew Schook Eun Joo Song Michael S. Marshall Michael S. Marshall Michael S. Marshall Joseph S. Takahashi Joseph S. Takahashi Joseph S. Takahashi |
| author_facet | Aaron E. Schirmer Aaron E. Schirmer Vivek Kumar Vivek Kumar Andrew Schook Eun Joo Song Michael S. Marshall Michael S. Marshall Michael S. Marshall Joseph S. Takahashi Joseph S. Takahashi Joseph S. Takahashi |
| author_sort | Aaron E. Schirmer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T05:38:15Z |
| format | Article |
| id | doaj.art-15fd009a5c6f4aa496c75024062fa23e |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-03-13T05:38:15Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-15fd009a5c6f4aa496c75024062fa23e2023-06-14T04:42:15ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-06-011710.3389/fnins.2023.11661371166137Cry1 expression during postnatal development is critical for the establishment of normal circadian periodAaron E. Schirmer0Aaron E. Schirmer1Vivek Kumar2Vivek Kumar3Andrew Schook4Eun Joo Song5Michael S. Marshall6Michael S. Marshall7Michael S. Marshall8Joseph S. Takahashi9Joseph S. Takahashi10Joseph S. Takahashi11Department of Neurobiology, Northwestern University, Evanston, IL, United StatesDepartment of Biology, Northeastern Illinois University, Chicago, IL, United StatesDepartment of Neurobiology, Northwestern University, Evanston, IL, United StatesThe Jackson Laboratory, Bar Harbor, ME, United StatesDepartment of Neurobiology, Northwestern University, Evanston, IL, United StatesDepartment of Neurobiology, Northwestern University, Evanston, IL, United StatesDepartment of Neurobiology, Northwestern University, Evanston, IL, United StatesDepartment of Pathology, Massachusetts General Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDepartment of Neurobiology, Northwestern University, Evanston, IL, United StatesDepartment of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, United StatesHoward Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, United StatesThe 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.https://www.frontiersin.org/articles/10.3389/fnins.2023.1166137/fullcryptochromecircadian rhythmsperiod lengthdevelopmentgene expression |
| spellingShingle | Aaron E. Schirmer Aaron E. Schirmer Vivek Kumar Vivek Kumar Andrew Schook Eun Joo Song Michael S. Marshall Michael S. Marshall Michael S. Marshall Joseph S. Takahashi Joseph S. Takahashi Joseph S. Takahashi Cry1 expression during postnatal development is critical for the establishment of normal circadian period Frontiers in Neuroscience cryptochrome circadian rhythms period length development gene expression |
| title | Cry1 expression during postnatal development is critical for the establishment of normal circadian period |
| title_full | Cry1 expression during postnatal development is critical for the establishment of normal circadian period |
| title_fullStr | Cry1 expression during postnatal development is critical for the establishment of normal circadian period |
| title_full_unstemmed | Cry1 expression during postnatal development is critical for the establishment of normal circadian period |
| title_short | Cry1 expression during postnatal development is critical for the establishment of normal circadian period |
| title_sort | cry1 expression during postnatal development is critical for the establishment of normal circadian period |
| topic | cryptochrome circadian rhythms period length development gene expression |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1166137/full |
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