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These oscillations are based on transcriptional feedback loops of clock genes, which in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    include the transcriptional activators\n                    <jats:italic>Clock (Clk)<\/jats:italic>\n                    and\n                    <jats:italic>cycle (cyc)<\/jats:italic>\n                    . While the mechanisms underlying this molecular clock are very well characterized, the roles that the core clock genes play in neuronal physiology and development are much less understood. The\n                    <jats:italic>Drosophila<\/jats:italic>\n                    timekeeping center is composed of ~150 clock neurons, among which the four small ventral lateral neurons (sLN\n                    <jats:sub>v<\/jats:sub>\n                    s) are the most dominant pacemakers under constant conditions. Here, we show that downregulating the clock gene\n                    <jats:italic>cyc<\/jats:italic>\n                    specifically in the\n                    <jats:italic>Pdf<\/jats:italic>\n                    -expressing neurons leads to decreased fasciculation both in larval and adult brains. This effect is due to a developmental role of\n                    <jats:italic>cyc<\/jats:italic>\n                    , as both knocking down\n                    <jats:italic>cyc<\/jats:italic>\n                    or expressing a dominant negative form of\n                    <jats:italic>cyc<\/jats:italic>\n                    exclusively during development lead to defasciculation phenotypes in adult clock neurons.\n                    <jats:italic>Clk<\/jats:italic>\n                    downregulation also leads to developmental effects on sLNv morphology. Our results reveal a non-circadian role for\n                    <jats:italic>cyc<\/jats:italic>\n                    , shedding light on the additional functions of circadian clock genes in the development of the nervous system.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1011441","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T13:39:53Z","timestamp":1729517993000},"page":"e1011441","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Drosophila circadian clock gene cycle controls the development of clock neurons"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6677-6499","authenticated-orcid":true,"given":"Grace","family":"Biondi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"McCormick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-6114","authenticated-orcid":true,"given":"Maria P.","family":"Fernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"issue":"10","key":"pgen.1011441.ref001","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrn2215","article-title":"Neurons and networks in daily rhythms.","volume":"8","author":"ED Herzog","year":"2007","journal-title":"Nat Rev Neurosci"},{"issue":"1","key":"pgen.1011441.ref002","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.neuron.2012.08.035","article-title":"Peptide neuromodulation in invertebrate model systems","volume":"76","author":"PH Taghert","year":"2012","journal-title":"Neuron"},{"issue":"4","key":"pgen.1011441.ref003","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1073\/pnas.89.4.1423","article-title":"Ontogeny of a biological clock in Drosophila melanogaster","volume":"89","author":"A Sehgal","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pgen.1011441.ref004","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/jemt.10357","article-title":"The neuroarchitecture of the circadian clock in the brain of Drosophila melanogaster","volume":"62","author":"C. 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