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The regulation of circadian rhythms and downstream processes is highly dependent on the proper development and function of the SCN.\n                    <jats:italic>Six3<\/jats:italic>\n                    and\n                    <jats:italic>Six6<\/jats:italic>\n                    are homologous homeodomain transcription factors that have been shown to be required for SCN development; intriguingly, both\n                    <jats:italic>Six3<\/jats:italic>\n                    and\n                    <jats:italic>Six6<\/jats:italic>\n                    remain expressed in the adult SCN. To determine the role of\n                    <jats:italic>Six3<\/jats:italic>\n                    and\n                    <jats:italic>Six6<\/jats:italic>\n                    in the SCN after neurogenesis, we used Cre\u2010lox to conditionally knockdown either\n                    <jats:italic>Six3<\/jats:italic>\n                    or\n                    <jats:italic>Six6<\/jats:italic>\n                    from cells that express neuromedin\u2010S (NMS), a neuropeptide expressed in approximately half of SCN neurons. We found that the\n                    <jats:italic>Nms<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>cre<\/jats:italic>\n                    <\/jats:sup>\n                    allele turns on in the SCN after embryonic Day 16.5, limiting Cre\u2010lox\u2010mediated loss of\n                    <jats:italic>Six3<\/jats:italic>\n                    or\n                    <jats:italic>Six6<\/jats:italic>\n                    to the period after SCN neurogenesis. Using this approach, we hypothesized that\n                    <jats:italic>Six3<\/jats:italic>\n                    and\n                    <jats:italic>Six6<\/jats:italic>\n                    in NMS neurons regulate SCN circadian output and resulting reproductive function in males and females. Loss of\n                    <jats:italic>Six6<\/jats:italic>\n                    from NMS neurons had no impact on puberty and reproduction. While loss of\n                    <jats:italic>Six3<\/jats:italic>\n                    from NMS neurons had no effect in females, we found significantly decreased sperm motility in males, potentially through direct effects of\n                    <jats:italic>Six3<\/jats:italic>\n                    in the testis. Loss of\n                    <jats:italic>Six3,<\/jats:italic>\n                    but not\n                    <jats:italic>Six6<\/jats:italic>\n                    , in NMS neurons resulted in shortened wheel\u2010running periods in constant darkness, indicating a shortening of the endogenous rhythm within the SCN. Together, these data indicate a role of\n                    <jats:italic>Six3<\/jats:italic>\n                    in determining the circadian period, suggesting differing functions of\n                    <jats:italic>Six3<\/jats:italic>\n                    and\n                    <jats:italic>Six6<\/jats:italic>\n                    in the adult SCN.\n                  <\/jats:p>","DOI":"10.1002\/jnr.70123","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:25:18Z","timestamp":1775449518000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Transcription Factors\n                    <i>Six3<\/i>\n                    and\n                    <i>Six6<\/i>\n                    in Neuromedin\u2010S Neurons Differentially Affect Circadian Rhythms"],"prefix":"10.1002","volume":"104","author":[{"given":"Brooke M.","family":"Van 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