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PMID:21525287

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Citation

VanDunk, C, Hunter, LA and Gray, PA (2011) Development, maturation, and necessity of transcription factors in the mouse suprachiasmatic nucleus. J. Neurosci. 31:6457-67

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.

Links

PubMed PMC3106226 Online version:10.1523/JNEUROSCI.5385-10.2011

Keywords

Animals; Animals, Newborn; Circadian Rhythm/genetics; Circadian Rhythm/physiology; Eye Proteins/genetics; Female; Gene Expression Regulation, Developmental/genetics; Gene Expression Regulation, Developmental/physiology; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Intermediate Filament Proteins/genetics; LIM-Homeodomain Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins/genetics; Neuroepithelial Cells/metabolism; Nuclear Receptor Subfamily 1, Group F, Member 1/genetics; RNA, Messenger/metabolism; Suprachiasmatic Nucleus/cytology; Suprachiasmatic Nucleus/embryology; Suprachiasmatic Nucleus/growth & development; Suprachiasmatic Nucleus/metabolism; Trans-Activators/genetics; Trans-Activators/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Vasoactive Intestinal Peptide/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SIX3

acts_upstream_of_or_within

GO:0048512: circadian behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3693321

P

Seeded From UniProt

complete


See also

References

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