Dissection of central clock function in Drosophila through cell-specific CRISPR-mediated clock gene disruption
In Drosophila, ~150 neurons expressing molecular clock proteins regulate circadian behavior. Sixteen of these neurons secrete the neuropeptide Pdf and have been called ‘master pacemakers’ because they are essential for circadian rhythms. A subset of Pdf+ neurons (the morning oscillator) regulates mo...
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2019-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/48308 |
| _version_ | 1818026943311773696 |
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| author | Rebecca Delventhal Reed M O'Connor Meghan M Pantalia Matthew Ulgherait Han X Kim Maylis K Basturk Julie C Canman Mimi Shirasu-Hiza |
| author_facet | Rebecca Delventhal Reed M O'Connor Meghan M Pantalia Matthew Ulgherait Han X Kim Maylis K Basturk Julie C Canman Mimi Shirasu-Hiza |
| author_sort | Rebecca Delventhal |
| collection | DOAJ |
| description | In Drosophila, ~150 neurons expressing molecular clock proteins regulate circadian behavior. Sixteen of these neurons secrete the neuropeptide Pdf and have been called ‘master pacemakers’ because they are essential for circadian rhythms. A subset of Pdf+ neurons (the morning oscillator) regulates morning activity and communicates with other non-Pdf+ neurons, including a subset called the evening oscillator. It has been assumed that the molecular clock in Pdf+ neurons is required for these functions. To test this, we developed and validated Gal4-UAS based CRISPR tools for cell-specific disruption of key molecular clock components, period and timeless. While loss of the molecular clock in both the morning and evening oscillators eliminates circadian locomotor activity, the molecular clock in either oscillator alone is sufficient to rescue circadian locomotor activity in the absence of the other. This suggests that clock neurons do not act in a hierarchy but as a distributed network to regulate circadian activity. |
| first_indexed | 2024-12-10T04:40:02Z |
| format | Article |
| id | doaj.art-bc7e0b4937834d64871be6d898373b6b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:40:02Z |
| publishDate | 2019-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-bc7e0b4937834d64871be6d898373b6b2022-12-22T02:01:55ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.48308Dissection of central clock function in Drosophila through cell-specific CRISPR-mediated clock gene disruptionRebecca Delventhal0https://orcid.org/0000-0002-0920-0004Reed M O'Connor1https://orcid.org/0000-0001-6025-772XMeghan M Pantalia2https://orcid.org/0000-0001-9932-4926Matthew Ulgherait3Han X Kim4Maylis K Basturk5Julie C Canman6https://orcid.org/0000-0001-8135-2072Mimi Shirasu-Hiza7https://orcid.org/0000-0002-2730-1765Department of Genetics and Development, Columbia University Medical Center, New York, United StatesDepartment of Genetics and Development, Columbia University Medical Center, New York, United StatesDepartment of Genetics and Development, Columbia University Medical Center, New York, United StatesDepartment of Genetics and Development, Columbia University Medical Center, New York, United StatesDepartment of Genetics and Development, Columbia University Medical Center, New York, United StatesDepartment of Genetics and Development, Columbia University Medical Center, New York, United StatesDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, United StatesDepartment of Genetics and Development, Columbia University Medical Center, New York, United StatesIn Drosophila, ~150 neurons expressing molecular clock proteins regulate circadian behavior. Sixteen of these neurons secrete the neuropeptide Pdf and have been called ‘master pacemakers’ because they are essential for circadian rhythms. A subset of Pdf+ neurons (the morning oscillator) regulates morning activity and communicates with other non-Pdf+ neurons, including a subset called the evening oscillator. It has been assumed that the molecular clock in Pdf+ neurons is required for these functions. To test this, we developed and validated Gal4-UAS based CRISPR tools for cell-specific disruption of key molecular clock components, period and timeless. While loss of the molecular clock in both the morning and evening oscillators eliminates circadian locomotor activity, the molecular clock in either oscillator alone is sufficient to rescue circadian locomotor activity in the absence of the other. This suggests that clock neurons do not act in a hierarchy but as a distributed network to regulate circadian activity.https://elifesciences.org/articles/48308CRISPR/Cas9GAL4/UAScircadian rhythm |
| spellingShingle | Rebecca Delventhal Reed M O'Connor Meghan M Pantalia Matthew Ulgherait Han X Kim Maylis K Basturk Julie C Canman Mimi Shirasu-Hiza Dissection of central clock function in Drosophila through cell-specific CRISPR-mediated clock gene disruption eLife CRISPR/Cas9 GAL4/UAS circadian rhythm |
| title | Dissection of central clock function in Drosophila through cell-specific CRISPR-mediated clock gene disruption |
| title_full | Dissection of central clock function in Drosophila through cell-specific CRISPR-mediated clock gene disruption |
| title_fullStr | Dissection of central clock function in Drosophila through cell-specific CRISPR-mediated clock gene disruption |
| title_full_unstemmed | Dissection of central clock function in Drosophila through cell-specific CRISPR-mediated clock gene disruption |
| title_short | Dissection of central clock function in Drosophila through cell-specific CRISPR-mediated clock gene disruption |
| title_sort | dissection of central clock function in drosophila through cell specific crispr mediated clock gene disruption |
| topic | CRISPR/Cas9 GAL4/UAS circadian rhythm |
| url | https://elifesciences.org/articles/48308 |
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