Development, Maturation, and Necessity of Transcription Factors in the Mouse Suprachiasmatic Nucleus
Open accessAbstract
The suprachiasmatic nucleus (SCN) of the hypothalamus is the master mammalian circadian clock. The SCN is highly specialized because it is responsible for generating a near 24 h rhythm, integrating external cues, and translating the rhythm throughout the body. Currently, our understanding of the developmental origin and genetic program involved in the proper specification and maturation of the SCN is limited. Herein, we provide a detailed analysis of transcription factor (TF) and developmental-gene expression in the SCN from neurogenesis to adulthood in mice (Mus musculus). TF expression within the postmitotic SCN was not static but rather showed specific temporal and spatial changes during prenatal and postnatal development. In addition, we found both global and regional patterns of TF expression extending into the adult. We found that the SCN is derived from a distinct region of the neuroepithelium expressing a combination of developmental genes: Six3, Six6, Fzd5, and transient Rx, allowing us to pinpoint the origin of this region within the broader developing telencephalon/diencephalon. We tested the necessity of two TFs in SCN development, RORα and Six3, which were expressed during SCN development, persisted into adulthood, and showed diurnal rhythmicity. Loss of RORα function had no effect on SCN peptide expression or localization. In marked contrast, the conditional deletion of Six3 from early neural progenitors completely eliminated the formation of the SCN. Our results provide the first description of the involvement of TFs in the specification and maturation of a neural population necessary for circadian behavior.
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By mid-to-late gestation, rhythms of metabolic activity and gene expression are evident in the SCN of rodents and non-human primates.
“By mid-to-late gestation, rhythms of metabolic activity and gene expression are evident in the SCN of rodents and NHPs23–25; however, the functional importance of early prenatal development of the SCN for fetal rhythms and physiology is less well understood.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [25]
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Cites
Genome-wide atlas of gene expression in the adult mouse brain
Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., et al. (2007) · Nature · doi:10.1038/nature05453 · Cited by 5,572 · see citing works
A gene expression atlas of the central nervous system based on bacterial artificial chromosomes
Gong, S., Zheng, C., Doughty, M. L., Losos, K., Didkovsky, N., Schambra, U. B., Nowak, N. J., Joyner, A., Leblanc, G., Hatten, M. E., et al. (2003) · Nature · doi:10.1038/nature02033 · Cited by 2,108 · see citing works
Interacting molecular loops in the mammalian circadian clock
Shearman, L. P., Sriram, S., Weaver, D. R., Maywood, E. S., Chaves, I., Zheng, B., Kume, K., Lee, C. C., van der, G. T. J., Horst, et al. (2000) · Science · doi:10.1126/science.288.5468.1013 · Cited by 1,367 · see citing works
A Functional Genomics Strategy Reveals Rora as a Component of the Mammalian Circadian Clock
Sato, T. K., Panda, S., Miraglia, L. J., Reyes, T. M., Rudic, R. D., McNamara, P., Naik, K. A., FitzGerald, G. A., Kay, S. A., & Hogenesch, J. B. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.018 · Cited by 1,115 · see citing works
Abrahamson, E. E., & Moore, R. Y. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02890-6 · Cited by 788 · see citing works
Oliver, G. C., Mailhos, A., Wehr, R., Copeland, N. G., Jenkins, N. A., & Gruß, P. (1995) · Development · doi:10.1242/dev.121.12.4045 · Cited by 674 · see citing works
A High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo
Diez-Roux, G., Banfi, S., Sultan, M., Geffers, L., Anand, S., Rozado, D., Magen, A., Canidio, E., Pagani, M., Peluso, I., et al. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1000582 · Cited by 638 · see citing works
GenePaint.org: an atlas of gene expression patterns in the mouse embryo
Visel, A. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh029 · Cited by 528 · see citing works
Lagutin, O. V., Zhu, C. C., Kobayashi, D., Topczewski, J., Shimamura, K., Puelles, L., Russell, H. R. C., McKinnon, P. J., Solnica‐Krezel, L., & Oliver, G. C. (2003) · Genes & Development · doi:10.1101/gad.1059403 · Cited by 528 · see citing works
Disruption of the nuclear hormone receptor RORα in staggerer mice
Hamilton, B. A., Frankel, W. N., Kerrebrock, A. W., Hawkins, T. L., FitzHugh, W., Kusumi, K., Russell, L. B., Mueller, K. L., van Berkel, V. H., Birren, B. W., et al. (1996) · Nature · doi:10.1038/379736a0 · Cited by 492 · see citing works
A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity
Dasen, J. S., Tice, B. C., Brenner-Morton, S., & Jessell, T. M. (2005) · Cell · doi:10.1016/j.cell.2005.09.009 · Cited by 461 · see citing works
Mouse Brain Organization Revealed Through Direct Genome-Scale TF Expression Analysis
Gray, P. A., Fu, H. Q., Luo, P., Zhao, Q., Yu, J., Ferrari, A., Tenzen, T., Yuk, D., Tsung, E. F., Cai, Z., et al. (2004) · Science · doi:10.1126/science.1104935 · Cited by 413 · see citing works
Self-citationA genomic atlas of mouse hypothalamic development
Shimogori, T., Lee, D. A., Miranda-Angulo, A., Yang, Y., Wang, H., Jiang, L., Yoshida, A. C., Kataoka, A., Mashiko, H., Avetisyan, M., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2545 · Cited by 382 · see citing works
Organization of neural inputs to the suprachiasmatic nucleus in the rat
Moga, M. M., & Moore, R. Y. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19971222)389:3 · Cited by 308 · see citing works
Altman, J., & Bayer, S. A. (1978) · The Journal of Comparative Neurology · doi:10.1002/cne.901820511 · Cited by 306 · see citing works
Topographic organization of suprachiasmatic nucleus projection neurons
Leak, R. K., & Moore, R. Y. (2001) · The Journal of Comparative Neurology · doi:10.1002/cne.1142 · Cited by 295 · see citing works
Carlberg, C., van Huijsduijnen, R. H., Staple, J. K., DeLamarter, J. F., & Becker-André, M. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.6.7935491 · Cited by 258 · see citing works
Becker-André, M., André, E., & DeLamarter, J. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1976 · Cited by 250 · see citing works
Direct interaction of geminin and Six3 in eye development
Bene, F. D., Tessmar‐Raible, K., & Wittbrodt, J. (2004) · Nature · doi:10.1038/nature02292 · Cited by 240 · see citing works
Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons
Webb, A. B., Angelo, N., Huettner, J. E., & Herzog, E. D. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902768106 · Cited by 236 · see citing works
Early subdivisions in the neural plate define distinct competence for inductive signals
Kobayashi, D., Kobayashi, M., Matsumoto, K., Ogura, T., Nakafuku, M., & Shimamura, K. (2002) · Development · doi:10.1242/dev.129.1.83 · Cited by 224 · see citing works
Hamada, T., LeSauter, J., Venuti, J. M., & Silver, R. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07742.2001 · Cited by 222 · see citing works
Reppert, S., & Schwartz, W. J. (1984) · Journal of Neuroscience · doi:10.1523/jneurosci.04-07-01677.1984 · Cited by 215 · see citing works
The Development of the Rat Hypothalamus
Altman, J., & Bayer, S. A. (1986) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-642-71301-9 · Cited by 202 · see citing works
Wang, W., & Lufkin, T. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9902 · Cited by 197 · see citing works
Time of neuron origin in mouse hypothalamic nuclei
Shimada, M., & Nakamura, T. (1973) · Experimental Neurology · doi:10.1016/0014-4886(73)90187-8 · Cited by 188 · see citing works
Altman, J., & Bayer, S. A. (1986) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-642-71301-9_1 · Cited by 188 · see citing works
Simeone, A., D’Apice, M. R., Nigro, V., Casanova, J., Graziani, F., Acampora, D., & Avantaggiato, V. (1994) · Neuron · doi:10.1016/0896-6273(94)90461-8 · Cited by 187 · see citing works
Jean, D., Bernier, G., & Gruß, P. (1999) · Mechanisms of Development · doi:10.1016/s0925-4773(99)00068-4 · Cited by 184 · see citing works
Orphan nuclear receptor RORα-deficient mice display the cerebellar defects of staggerer
Dussault, I., Fawcett, D., Matthyssen, A., Bader, J.-A., & Giguère, V. (1998) · Mechanisms of Development · doi:10.1016/s0925-4773(97)00187-1 · Cited by 174 · see citing works
Regulation of vertebrate eye development by Rx genes
Bailey, T. J., El‐Hodiri, H. M., Zhang, L., Shah, R., Mathers, E. H., & Jamrich, M. (2004) · The International Journal of Developmental Biology · doi:10.1387/ijdb.041878tb · Cited by 172 · see citing works
Six3 activation of Pax6 expression is essential for mammalian lens induction and specification
Liu, W., Lagutin, O. V., Mende, M., Streit, A., & Oliver, G. C. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601398 · Cited by 163 · see citing works
Molecular mechanisms of pituitary organogenesis: In search of novel regulatory genes
Davis, S. W., Castinetti, F., Carvalho, L. R. S., Ellsworth, B. S., Potok, M. A., Lyons, R. H., Brinkmeier, M. L., Raetzman, L. T., Carninci, P., Mortensen, A. H., et al. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.12.012 · Cited by 163 · see citing works
Seo, H., Curtiss, J., Mlodzik, M., & Fjose, A. (1999) · Mechanisms of Development · doi:10.1016/s0925-4773(99)00045-3 · Cited by 161 · see citing works
Schaeren‐Wiemers, N., André, É., Kapfhammer, J. P., & Becker-André, M. (1997) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1997.tb01698.x · Cited by 159 · see citing works
Gradients in the circadian expression of Per1 and Per2 genes in the rat suprachiasmatic nucleus
Yan, L., & Okamura, H. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.01955.x · Cited by 146 · see citing works
Sládek, M., Sumová, A., Kovačíková, Z., Bendová, Z., Laurinová, K., & Illnerová, H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401149101 · Cited by 145 · see citing works
Oishi, K., Fukui, H., & Ishida, N. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.2054 · Cited by 140 · see citing works
Hamada, T., Antle, M. C., & Silver, R. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03275.x · Cited by 127 · see citing works
Nakagawa, Y., & O’Leary, D. D. M. (2003) · Developmental Neuroscience · doi:10.1159/000072271 · Cited by 121 · see citing works
Phenotype Matters: Identification of Light-Responsive Cells in the Mouse Suprachiasmatic Nucleus
Karatsoreos, I. N., Yan, L., LeSauter, J., & Silver, R. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1666-03.2004 · Cited by 121 · see citing works
Liu, W., Lagutin, O. V., Swindell, E. C., Jamrich, M., & Oliver, G. C. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43219 · Cited by 109 · see citing works
Development of neuronal activity in the rat suprachiasmatic nucleus
Shibata, S., & Moore, R. Y. (1987) · Developmental Brain Research · doi:10.1016/0165-3806(87)90220-3 · Cited by 108 · see citing works
Gestri, G., Carl, M., Appolloni, I., Wilson, S. W., Barsacchi, G., & Andreazzoli, M. (2005) · Development · doi:10.1242/dev.01814 · Cited by 95 · see citing works
Transcription factors and the genetic organization of brain stem respiratory neurons
Gray, P. A. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01383.2007 · Cited by 94 · see citing works
Self-citationDevelopment of melanopsin-based irradiance detecting circuitry
McNeill, D. S., Sheely, C. J., Ecker, J. L., Badea, T. C., Morhardt, D. R., Guido, W., & Hattar, S. S. (2011) · Neural Development · doi:10.1186/1749-8104-6-8 · Cited by 92 · see citing works
Development of Vasoactive Intestinal Peptide mRNA Rhythm in the Rat Suprachiasmatic Nucleus
Ban, Y., Shigeyoshi, Y., & Okamura, H. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-10-03920.1997 · Cited by 90 · see citing works
The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene
Tucker, P. K., Laemle, L. K., Munson, A. M., Kanekar, S., Oliver, E. R., Brown, N. L., Schlecht, H. P., Vetter, M. L., & Glaser, T. M. (2001) · genesis · doi:10.1002/gene.10003 · Cited by 85 · see citing works
Kovačíková, Z., Sládek, M., Bendová, Z., Illnerová, H., & Sumová, A. (2006) · Journal of Biological Rhythms · doi:10.1177/0748730405285876 · Cited by 78 · see citing works
Sumová, A., Bendová, Z., Mikkelsen, J. D., & Illnerová, H. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00619-2 · Cited by 75 · see citing works
Matysiak‐Scholze, U., & Nehls, M. C. (1997) · Genomics · doi:10.1006/geno.1997.4757 · Cited by 74 · see citing works
Dlx transcription factors regulate differentiation of dopaminergic neurons of the ventral thalamus
Andrews, G. L., Yun, K., Rubenstein, J. L. R., & Mastick, G. S. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(03)00016-2 · Cited by 74 · see citing works
Lavado, A., Lagutin, O. V., & Oliver, G. C. (2007) · Development · doi:10.1242/dev.010082 · Cited by 72 · see citing works
Invited Review: A neural clockwork for encoding circadian time
Herzog, E. D., & Schwartz, W. J. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00836.2001 · Cited by 71 · see citing works
Repression of Six3 by a corepressor regulates rhodopsin expression
Manavathi, B., Peng, S., Rayala, S. K., Talukder, A. H., Wang, M. H., Wang, R., Balasenthil, S., Agarwal, N. A., Frishman, L. J., & Kumar, R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705878104 · Cited by 67 · see citing works
Investigation of Frizzled‐5 during embryonic neural development in mouse
Burns, C. J., Zhang, J., Brown, E. C., Bibber, A. M. V., van Es, J. H., Clevers, H. C., Ishikawa, T., Taketo, M. M., Vetter, M. L., & Fuhrmann, S. (2008) · Developmental Dynamics · doi:10.1002/dvdy.21565 · Cited by 61 · see citing works
Schmidt, J. T., Buzzard, M., Borress, R., & Dhillon, S. (2000) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(20000215)42:3 · Cited by 60 · see citing works
Prominent expression of nuclear hormone receptor RORα in Purkinje cells from early development
Nakagawa, S., Watanabe, M., & Inoue, Y. (1997) · Neuroscience Research · doi:10.1016/s0168-0102(97)00042-4 · Cited by 55 · see citing works
Daily Rhythm of Spontaneous Immediate-Early Gene Expression in the Rat Suprachiasmatic Nucleus
Guido, M. E., de Guido, L., Goguen, D., Robertson, H. A., & Rusak, B. (1999) · Journal of Biological Rhythms · doi:10.1177/074873099129000687 · Cited by 51 · see citing works
Okamura, H., Fukui, K., Koyama, E., Tsutou, H. L. O., Tsutou, T., Terubayashi, H., Fujisawa, H., & Ibata, Y. (1983) · Developmental Brain Research · doi:10.1016/0165-3806(83)90055-x · Cited by 46 · see citing works
Setting the biological time in central and peripheral clocks during ontogenesis
Sumová, A., Bendová, Z., Sládek, M., El‐Hennamy, R. E., Laurinová, K., Jindráková, Z., & Illnerová, H. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.03.023 · Cited by 45 · see citing works
Silver, J. (1977) · The Journal of Comparative Neurology · doi:10.1002/cne.901760409 · Cited by 43 · see citing works
Kabrita, C. S., & Davis, F. C. (2007) · Brain Research · doi:10.1016/j.brainres.2007.12.020 · Cited by 42 · see citing works
Ramanathan, C., Núñez, A. A., Martínez, G. S., Schwartz, M. D., & Smale, L. (2006) · Brain Research · doi:10.1016/j.brainres.2005.11.082 · Cited by 41 · see citing works
Neurogenesis of the hamster suprachiasmatic nucleus
Davis, F. C., Boada, R., & LeDeaux, J. R. (1990) · Brain Research · doi:10.1016/0006-8993(90)90077-o · Cited by 37 · see citing works
Rhythmic expression of RORβ mRNA in the mice suprachiasmatic nucleus
Sumi, Y., Yagita, K., Yamaguchi, S., Ishida, Y., Kuroda, Y., & Okamura, H. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00011-3 · Cited by 33 · see citing works
Neurogenesis and ontogeny of specific cell phenotypes within the hamster suprachiasmatic nucleus
Antle, M. C., LeSauter, J., & Silver, R. (2005) · Developmental Brain Research · doi:10.1016/j.devbrainres.2005.02.017 · Cited by 33 · see citing works
Towards the integration of spatially and temporally resolved murine gene expression databases
Sunkin, S. M. (2006) · Trends in Genetics · doi:10.1016/j.tig.2006.02.006 · Cited by 31 · see citing works
Romero, M.-T., & Silver, R. (1990) · Developmental Brain Research · doi:10.1016/0165-3806(90)90177-z · Cited by 28 · see citing works
A Nonautonomous Role for Retinal Frizzled-5 in Regulating Hyaloid Vitreous Vasculature Development
Zhang, J., Fuhrmann, S., & Vetter, M. L. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-2226 · Cited by 27 · see citing works
Bendová, Z., Sumová, A., & Illnerová, H. (2004) · Developmental Brain Research · doi:10.1016/j.devbrainres.2003.10.007 · Cited by 26 · see citing works
Kovačíková, Z., Sládek, M., Laurinová, K., Bendová, Z., Illnerová, H., & Sumová, A. (2005) · Brain Research · doi:10.1016/j.brainres.2005.10.022 · Cited by 16 · see citing works
A relationship between substance P receptor and retinal fibers in the rat suprachiasmatic nucleus
Takatsuji, K., Senba, E., Mantyh, P. W., & Tohyama, M. (1995) · Brain Research · doi:10.1016/0006-8993(95)00802-w · Cited by 15 · see citing works
Isobe, Y., Nakajima, K., & Nishino, H. (1995) · Developmental Brain Research · doi:10.1016/0165-3806(94)00192-3 · Cited by 14 · see citing works
Circadian and developmental regulation of Oct-2 gene expression in the suprachiasmatic nuclei.
Rivkees, S., Weaver, D., & Reppert, S. (1992) · Brain Research · doi:10.1016/0006-8993(92)90203-l · Cited by 13 · see citing works
Herzog, E. D., & Schwartz, W. J. (2002) · Cited by 9 · see citing works
Flagged first, then by citations
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Kriks, S., Shim, J., Piao, J., Ganat, Y. M., Wakeman, D. R., Xie, Z., Carrillo‐Reid, L., Auyeung, G., Antonacci, C. L., Buch, A., et al. (2011) · Nature · doi:10.1038/nature10648 · Cited by 1,912 · see citing works
Rhythms of life: circadian disruption and brain disorders across the lifespan
Logan, R. W., & McClung, C. A. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0088-y · Cited by 713 · see citing works
Single-Cell RNA-Seq Reveals Hypothalamic Cell Diversity
Chen, R., Wu, X., Jiang, L., & Zhang, Y. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.004 · Cited by 592 · see citing works
Mogha, A., Benesh, A. E., Patra, C., Engel, F. B., Schöneberg, T., Liebscher, I., & Monk, K. R. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1809-13.2013 · Cited by 188 · see citing works
Development of the hypothalamus: conservation, modification and innovation
Xie, Y., & Dorsky, R. I. (2017) · Development · doi:10.1242/dev.139055 · Cited by 169 · see citing works
RORγ directly regulates the circadian expression of clock genes and downstream targets in vivo
Takeda, Y., Jothi, R., Birault, V., & Jetten, A. M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks630 · Cited by 146 · see citing works
The bilaterian forebrain: an evolutionary chimaera
Tosches, M. A., & Arendt, D. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.09.005 · Cited by 106 · see citing works
Patterning, specification, and differentiation in the developing hypothalamus
Bedont, J. L., Newman, E. A., & Blackshaw, S. (2015) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.187 · Cited by 109 · see citing works
Lhx1 Controls Terminal Differentiation and Circadian Function of the Suprachiasmatic Nucleus
Bedont, J. L., LeGates, T. A., Slat, E. A., Byerly, M. S., Wang, H., Hu, J., Rupp, A. C., Qian, J. X., Wong, G. W., Herzog, E. D., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.060 · Cited by 98 · see citing works
Ontogeny of Circadian Rhythms and Synchrony in the Suprachiasmatic Nucleus
Carmona‐Alcocer, V., Abel, J. H., Sun, T. C., Petzold, L. R., Doyle, F. J., Simms, C. L., & Herzog, E. D. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2006-17.2017 · Cited by 98 · see citing works
The Regulatory Factor ZFHX3 Modifies Circadian Function in SCN via an AT Motif-Driven Axis
Parsons, M. J., Brancaccio, M., Sethi, S., Maywood, E. S., Satija, R., Edwards, J. K., Jagannath, A., Couch, Y., Finelli, M. J., Smyllie, N. J., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.060 · Cited by 94 · see citing works
Phenylthiourea Specifically Reduces Zebrafish Eye Size
Li, Z., Ptak, D., Zhang, L., Walls, E. K., Zhong, W., & Leung, Y. F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040132 · Cited by 94 · see citing works
Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulationPreprint
Dalal, J. S., Roh, J. H., Maloney, S. E., Akuffo, A., Shah, S., Yuan, H., Wamsley, B., Jones, W. B., Strong, C. D. G., Gray, P. A., et al. (2013) · Genes & Development · doi:10.1101/gad.207654.112 · Cited by 92 · see citing works
Self-citationChew, K. S., Renna, J. M., McNeill, D. S., Fernandez, D. C., Keenan, W. T., Thomsen, M. B., Ecker, J. L., Loevinsohn, G. S., VanDunk, C., Vicarel, D. C., et al. (2017) · eLife · doi:10.7554/elife.22861 · Cited by 86 · see citing works
Self-citationConstructing the suprachiasmatic nucleus: a watchmaker's perspective on the central clockworks
Bedont, J. L., & Blackshaw, S. (2015) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2015.00074 · Cited by 88 · see citing works
Roles of Neuropeptides, VIP and AVP, in the Mammalian Central Circadian Clock
Ono, D., Honma, K., & Honma, S. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.650154 · Cited by 87 · see citing works
Lhx1 maintains synchrony among circadian oscillator neurons of the SCN
Hatori, M., Gill, S., Mure, L. S., Goulding, M., O'Leary, D. D. M., & Panda, S. (2014) · eLife · doi:10.7554/elife.03357 · Cited by 81 · see citing works
RaxIs a Selector Gene for Mediobasal Hypothalamic Cell Types
Lu, F., Kar, D., Gruenig, N., Zhang, Z. W., Cousins, N., Rodgers, H. M., Swindell, E. C., Jamrich, M., Schuurmans, C. J., Mathers, P. H., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0913-12.2013 · Cited by 79 · see citing works
Transcription factors define the neuroanatomical organization of the medullary reticular formation
Gray, P. A. (2013) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2013.00007 · Cited by 86 · see citing works
Self-citationEmbryonic development of circadian clocks in the mammalian suprachiasmatic nuclei
Landgraf, D., Koch, C. E., & Oster, H. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00143 · Cited by 60 · see citing works
Ontogenesis of peptidergic neurons within the genoarchitectonic map of the mouse hypothalamus
DÃaz, C., Morales-Delgado, N., & Puelles, L. (2015) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00162 · Cited by 58 · see citing works
Circadian system from conception till adulthood
Sumová, A., Sládek, M., Polidarová, L., Nováková, M., & Houdek, P. (2012) · Progress in brain research · doi:10.1016/b978-0-444-59427-3.00005-8 · Cited by 56 · see citing works
The Suprachiasmatic Nucleus at 50: Looking Back, Then Looking Forward
Ono, D., Weaver, D. R., Hastings, M. H., Honma, K., Honma, S., & Silver, R. (2024) · Journal of Biological Rhythms · doi:10.1177/07487304231225706 · Cited by 52 · see citing works
Embryonic Development of Circadian Oscillations in the Mouse Hypothalamus
Wreschnig, D., Dolatshad, H., & Davis, F. C. (2014) · Journal of Biological Rhythms · doi:10.1177/0748730414545086 · Cited by 47 · see citing works
Molecular-genetic Manipulation of the Suprachiasmatic Nucleus Circadian Clock
Hastings, M. H., Smyllie, N. J., & Patton, A. P. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.01.019 · Cited by 50 · see citing works
Cai, J., Schleidt, S. S., Pelta‐Heller, J., Hutchings, D., Cannarsa, G. J., & Iacovitti, L. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.01.012 · Cited by 44 · see citing works
Clark, D. D., Gorman, M. R., Hatori, M., Meadows, J. D., Panda, S., & Mellon, P. L. (2013) · Journal of Biological Rhythms · doi:10.1177/0748730412468084 · Cited by 42 · see citing works
Orquera, D. P., Nasif, S., Low, M. J., Rubinstein, M., & de Souza, F. S. J. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.05.021 · Cited by 39 · see citing works
Wilcox, A. G., Vizor, L., Parsons, M. J., Banks, G. T., & Nolan, P. M. (2017) · Journal of Biological Rhythms · doi:10.1177/0748730417722631 · Cited by 37 · see citing works
Retinoid-Related Orphan Receptor β and Transcriptional Control of Neuronal Differentiation
Liu, H. S., Aramaki, M., Fu, Y., & Forrest, D. (2016) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2016.11.009 · Cited by 34 · see citing works
Brown, L. A., Williams, J. A., Taylor, L., Thomson, R. J., Nolan, P. M., Foster, F., & Peirson, S. N. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx714 · Cited by 35 · see citing works
Circuit development in the master clock network of mammals
Carmona‐Alcocer, V., Rohr, K. E., Joye, D. A. M., & Evans, J. A. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14259 · Cited by 37 · see citing works
Foxd1 is required for terminal differentiation of anterior hypothalamic neuronal subtypes
Newman, E. A., Kim, D. W., Wan, J., Wang, J., Qian, J. X., & Blackshaw, S. (2018) · Developmental Biology · doi:10.1016/j.ydbio.2018.04.012 · Cited by 36 · see citing works
Berry, M. H., Moldavan, M. G., Garrett, T. R., Meadows, M. A., Cravetchi, O., White, E., Leffler, J., von Gersdorff, H., Wright, K. M., Allen, C. N., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36955-6 · Cited by 34 · see citing works
Circadian Rhythms in the Neuronal Network Timing the Luteinizing Hormone Surge
Tonsfeldt, K. J., Mellon, P. L., & Hoffmann, H. M. (2021) · Endocrinology · doi:10.1210/endocr/bqab268 · Cited by 34 · see citing works
Hozer, C., Pifferi, F., Aujard, F., & Perret, M. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01033 · Cited by 29 · see citing works
Molecular regulation of hypothalamic development and physiological functions
Gao, Y.-X., & Sun, T. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9367-z · Cited by 27 · see citing works
Circadian rhythms as modulators of brain health during development and throughout aging
Drunen, R. V., & Eckel‐Mahan, K. L. (2023) · Frontiers in Neural Circuits · doi:10.3389/fncir.2022.1059229 · Cited by 28 · see citing works
The Homeodomain Transcription Factors Vax1 and Six6 Are Required for SCN Development and Function
Pandolfi, E. C., Breuer, J. A., Huu, V. A. N., Talluri, T., Nguyen, D., Lee, J. S., Hu, R. J., Bharti, K., Skowronska‐Krawczyk, D., Gorman, M. R., et al. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01781-9 · Cited by 26 · see citing works
Directed Differentiation of V3 Interneurons from Mouse Embryonic Stem Cells
Xu, H. Y., & Sakiyama‐Elbert, S. E. (2015) · Stem Cells and Development · doi:10.1089/scd.2015.0122 · Cited by 24 · see citing works
Hoffmann, H. M., Meadows, J. D., Breuer, J. A., Yaw, A. M., Nguyen, D., Tonsfeldt, K. J., Chin, A. Y., Devries, B. M., Trang, C., Oosterhouse, H. J., et al. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24864 · Cited by 20 · see citing works
Genomic code for Sox2 binding uncovers its regulatory role in Six3 activation in the forebrain
Lee, B., Song, H., Rizzoti, K., Son, Y., Yoon, J., Baek, K., & Jeong, Y. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.06.016 · Cited by 20 · see citing works
Gao, J. L., Xu, G., & Xu, P. (2021) · BMC Genomics · doi:10.1186/s12864-021-08182-0 · Cited by 16 · see citing works
Hoffmann, H. M., Pandolfi, E. C., Larder, R., & Mellon, P. L. (2018) · Neuroendocrinology · doi:10.1159/000494086 · Cited by 16 · see citing works
Mystery of rhythmic signal emergence within the suprachiasmatic nuclei
Sumová, A., & Čečmanová, V. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14141 · Cited by 15 · see citing works
Wilcox, A. G., Bains, R. S., Williams, D. J., Joynson, E., Vizor, L., Oliver, P. L., Maywood, E. S., Hastings, M. H., Banks, G. T., & Nolan, P. M. (2021) · iScience · doi:10.1016/j.isci.2021.103142 · Cited by 14 · see citing works
Genesis of the Master Circadian Pacemaker in Mice
Cheng, A. H., & Cheng, H. M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.659974 · Cited by 13 · see citing works
Light Input to the Mammalian Circadian Clock
Dannerfjord, A. A., Brown, L. A., Foster, F., & Peirson, S. N. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0381-9_18 · Cited by 13 · see citing works
Rohde, K., Bering, T., Furukawa, T., & Rath, M. F. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14120 · Cited by 13 · see citing works
ArxIs Required for Specification of the Zona Incerta and Reticular Nucleus of the Thalamus
Sunnen, C. N., Simonet, J. C., Marsh, E. D., & Golden, J. A. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000048 · Cited by 11 · see citing works
Meadows, J. D., Breuer, J. A., Lavalle, S. N., Hirschenberger, M. R., Patel, M. M., Nguyen, D., Kim, A., Cassin, J., Gorman, M. R., Welsh, D. K., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101431 · Cited by 10 · see citing works
Beligala, D. H., De, A., & Geusz, M. E. (2018) · BioMed Research International · doi:10.1155/2018/3610603 · Cited by 9 · see citing works
A Window into Domain Amplification Through Piccolo in Teleost Fish
Nonet, M. L. (2012) · G3 Genes Genomes Genetics · doi:10.1534/g3.112.003624 · Cited by 8 · see citing works
Anticancer Properties of Curcumin and Interactions With the Circadian Timing System
De, A., Beligala, D. H., Birkholz, T. M., & Geusz, M. E. (2019) · Integrative Cancer Therapies · doi:10.1177/1534735419889154 · Cited by 8 · see citing works
Developmental patterning of peptide transcription in the central circadian clock in both sexes
Carmona‐Alcocer, V., Brown, L. S., Anchan, A., Rohr, K. E., & Evans, J. A. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1177458 · Cited by 7 · see citing works
SOX2 Regulates Neuronal Differentiation of the Suprachiasmatic Nucleus
Cheng, A. H., Fung, S. W., Hegazi, S., Abdalla, O. H. M. H., & Cheng, H. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010229 · Cited by 5 · see citing works
Spišská, V., Pačesová, D., Míková, H., Pohanová, P., Telenský, P., Novotný, J., & Bendová, Z. (2020) · Brain Research · doi:10.1016/j.brainres.2020.146952 · Cited by 5 · see citing works
Izumo, M., Cox, K. H., & Takahashi, J. S. (2026) · Neurobiology of Sleep and Circadian Rhythms · doi:10.1016/j.nbscr.2026.100143 · Cited by 4 · see citing works
Modeling the Influence of Synaptic Plasticity on After-effects
Foster, S., Christiansen, T., & Antle, M. C. (2019) · Journal of Biological Rhythms · doi:10.1177/0748730419871189 · Cited by 4 · see citing works
Beligala, D. H., De, A., Malik, A., Silver, R., Rimu, K., LeSauter, J., McQuillen, H. J., & Geusz, M. E. (2019) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2019.04.007 · Cited by 4 · see citing works
Bafna, A., Banks, G. T., Vasilyev, V., Dallmann, R., Hastings, M. H., & Nolan, P. M. (2025) · eLife · doi:10.7554/elife.102019 · Cited by 4 · see citing works
Evo-devo applied to sleep research: an approach whose time has come
Brown, R. E. (2024) · SLEEP Advances · doi:10.1093/sleepadvances/zpae040 · Cited by 3 · see citing works
Hirayama, M., Mure, L. S., Le, H. D., & Panda, S. (2024) · iScience · doi:10.1016/j.isci.2024.109051 · Cited by 3 · see citing works
Curtis, L., & Piggins, H. D. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16443 · Cited by 3 · see citing works
Bafna, A., Banks, G. T., Vasilyev, V., Dallmann, R., Hastings, M. H., & Nolan, P. M. (2025) · eLife · doi:10.7554/elife.102019.3 · Cited by 2 · see citing works
Winding the Clock: Development of Hypothalamic Structures Controlling Biological Timing and Sleep
Kim, D. W., & Blackshaw, S. (2020) · Masterclass in neuroendocrinology · doi:10.1007/978-3-030-40002-6_5 · Cited by 2 · see citing works
White, A. K., Drake, K. D., Porczak, A. E., Tirado-Mansilla, G., Lee, M. F., Hyatt, K. C., Chow, C., DeQuattro, T., Mickelsen, L. E., Sciolino, N. R., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.04.510883 · Cited by 2 · see citing works
The earliest circadian clock in the mammalian brain emerges in the embryonic choroid plexusPreprint
Vitet, H., Truong, V., & Myung, J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.09.675224 · Cited by 1 · see citing works
Händler, K., Sreenivasan, V. K. A., Pilorz, V., Martinez-Perez, C., Elorduy, I., Casas, T. J., Lehmann, M., Olano-Bringas, J., Escobar, L., Bengoa‐Vergniory, N., et al. (2026) · PLoS Biology · doi:10.1371/journal.pbio.3003870 · Cited by 1 · see citing works
Lee, A. R., Lamb, R., Chang, J. H., Erdmann-Gilmore, P., Lichti, C. F., Rohrs, H. W., Malone, J. P., Wairkar, Y. P., DiAntonio, A., Townsend, R. R., et al. (2012) · Journal of Proteome Research · doi:10.1021/pr300767a · Cited by 1 · see citing works
Organe des Hormonsystems und ihre Entstehung
Kleine, B., & Rossmanith, W. G. (2020) · Springer eBooks · doi:10.1007/978-3-662-58502-3_10 · Cited by 1 · see citing works
Bafna, A., Banks, G. T., Vasilyev, V., Dallmann, R., Hastings, M. H., & Nolan, P. M. (2025) · eLife · doi:10.7554/elife.102019.1 · Cited by 1 · see citing works
Interspace Encounters: Parkview Gardens
Marak, M. (2016) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k7pg1q0b
Carter, D. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/680082
Astrocytes in the mouse suprachiasmatic nuclei respond directly to glucocorticoids feedbackPreprint
Händler, K., Sreenivasan, V. K. A., Pilorz, V., Olano-Bringas, J., Escobar, L., Bengoa‐Vergniory, N., Oster, H., Spielmann, M., & Astiz, M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.04.583323
Bafna, A., Banks, G. T., Vasilyev, V., Dallmann, R., Hastings, M. H., & Nolan, P. M. (2025) · eLife · doi:10.7554/elife.102019.2
Nervous system evolution : insights from the sea urchin
Formery, L. (2019) · theses.fr (ABES) · doi:10.70675/146c0b8aza71az47ecza2c7zc12baf0f5794
RORα as a context-dependent transcriptional stabilizer in the nervous system
Zhang, H., Li, J., Liu, H., Hu, X., Zhang, S., Yu, Q., Kuang, G., Liu, L., Wang, Z., Yu, D., et al. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106970
- Authors
- VanDunk, C., Hunter, L. A., & Gray, P. A.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Gray, Paul A.
- ORCID
- Hunter, Lindsay A.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-04-27
- Volume
- 31
- Issue
- 17
- Pages
- 6457-6467
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3106226
- OpenAlex
- W2028674633
- Cited by
- 89
- References
- 77
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 1 · 2021: 19 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 7 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 8 · 2012: 5
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL089742)
- National Institute of General Medical Sciences (GM T32 GM009151)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- suprachiasmatic nucleus, circadian clock, transcription factors, neural development, Six3, RORα, developmental genes, neural progenitor cells, FZD5, daily rhythms, circadian activity, mice
- MeSH terms
- Homeobox Protein SIX3, Animals, Animals, Newborn, Circadian Rhythm, Eye Proteins, Female, Intermediate Filament Proteins, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, RNA, Messenger, Suprachiasmatic Nucleus, Transcription Factors, Vasoactive Intestinal Peptide, Trans-Activators, Homeodomain Proteins, Gene Expression Regulation, Developmental, Neuroepithelial Cells, Mice, Nuclear Receptor Subfamily 1, Group F, Member 1, LIM-Homeodomain Proteins, Nestin
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