Cited by 89Circadian rhythm and melatoninNeurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene Regulation

Development, Maturation, and Necessity of Transcription Factors in the Mouse Suprachiasmatic Nucleus

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VanDunk, Cassandra, Hunter, Lindsay A., Gray, Paul A.·2011·The Journal of Neuroscience

Abstract

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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Crossref · 10.1523/jneurosci.5385-10.2011

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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.”

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Authors
VanDunk, C., Hunter, L. A., & Gray, P. A.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Gray, Paul A.
Venue
The Journal of Neuroscience
Published
2011-04-27
Volume
31
Issue
17
Pages
6457-6467
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
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
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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