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The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice.
Hoffmann, Hanne M; Meadows, Jason D; Breuer, Joseph A; Yaw, Alexandra M; Nguyen, Duong; Tonsfeldt, Karen J; Chin, Austin Y; Devries, Brooke M; Trang, Crystal; Oosterhouse, Haley J; Lee, Jessica Sora; Doser, Jeffrey W; Gorman, Michael R; Welsh, David K; Mellon, Pamela L.
Afiliación
  • Hoffmann HM; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Meadows JD; Center for Circadian Biology, University of California, San Diego, La Jolla, CA, USA.
  • Breuer JA; Department of Animal Science and the Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI, USA.
  • Yaw AM; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Nguyen D; Center for Circadian Biology, University of California, San Diego, La Jolla, CA, USA.
  • Tonsfeldt KJ; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Chin AY; Center for Circadian Biology, University of California, San Diego, La Jolla, CA, USA.
  • Devries BM; Department of Animal Science and the Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI, USA.
  • Trang C; Department of Animal Science and the Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI, USA.
  • Oosterhouse HJ; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Lee JS; Center for Circadian Biology, University of California, San Diego, La Jolla, CA, USA.
  • Doser JW; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Gorman MR; Center for Circadian Biology, University of California, San Diego, La Jolla, CA, USA.
  • Welsh DK; Department of Animal Science and the Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI, USA.
  • Mellon PL; Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, USA.
J Neurosci Res ; 99(10): 2625-2645, 2021 10.
Article en En | MEDLINE | ID: mdl-34212416
The homeodomain transcription factors sine oculis homeobox 3 (Six3) and ventral anterior homeobox 1 (Vax1) are required for brain development. Their expression in specific brain areas is maintained in adulthood, where their functions are poorly understood. To identify the roles of Six3 and Vax1 in neurons, we conditionally deleted each gene using Synapsincre , a promoter targeting maturing neurons, and generated Six3syn and Vax1syn mice. Six3syn and Vax1syn females, but not males, had reduced fertility, due to impairment of the luteinizing hormone (LH) surge driving ovulation. In nocturnal rodents, the LH surge requires a precise timing signal from the brain's circadian pacemaker, the suprachiasmatic nucleus (SCN), near the time of activity onset. Indeed, both Six3syn and Vax1syn females had impaired rhythmic SCN output, which was associated with weakened Period 2 molecular clock function in both Six3syn and Vax1syn mice. These impairments were associated with a reduction of the SCN neuropeptide vasoactive intestinal peptide in Vax1syn mice and a modest weakening of SCN timekeeping function in both Six3syn and Vax1syn mice. Changes in SCN function were associated with mistimed peak PER2::LUC expression in the SCN and pituitary in both Six3syn and Vax1syn females. Interestingly, Six3syn ovaries presented reduced sensitivity to LH, causing reduced ovulation during superovulation. In conclusion, we have identified novel roles of the homeodomain transcription factors SIX3 and VAX1 in neurons, where they are required for proper molecular circadian clock function, SCN rhythmic output, and female fertility.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carrera / Núcleo Supraquiasmático / Neuropéptidos / Ritmo Circadiano / Proteínas de Homeodominio / Proteínas del Ojo / Fertilidad / Proteínas del Tejido Nervioso Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Neurosci Res Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carrera / Núcleo Supraquiasmático / Neuropéptidos / Ritmo Circadiano / Proteínas de Homeodominio / Proteínas del Ojo / Fertilidad / Proteínas del Tejido Nervioso Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Neurosci Res Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos