title: Circadian genes, xBmal1 and xNocturnin, modulate the timing and differentiation of somites in Xenopus laevis.
abstract: We have been investigating whether xBmal1 and xNocturnin play a role in somitogenesis, a cyclic developmental process with an ultradian period. Previous work from our lab shows that circadian genes (xPeriod1, xPeriod2, xBmal1, and xNocturnin) are expressed in developing somites. Somites eventually form the vertebrae, muscles of the back, and dermis. In Xenopus, a pair of somites is formed about every 50 minutes from anterior to posterior. We were intrigued by the co-localization of circadian genes in an embryonic tissue known to be regulated by an ultradian clock. Cyclic expression of genes involved in Notch signaling has been implicated in the somite clock. Disruption of Notch signaling in humans has been linked to skeletal defects in the vertebral column. We found that both depletion (morpholino) and overexpression (mRNA) of xBMAL1 protein (bHLH transcription factor) or xNOCTURNIN protein (deadenylase) on one side of the developing embryo led to a significant decrease in somite number with respect to the untreated side (p<0.001). These manipulations also significantly affect expression of a somite clock component (xESR9; p<0.05). We observed opposing effects on somite size. Depletion of xBMAL1 or xNOCTURNIN caused a statistically significant decrease in somite area (quantified using NIH ImageJ; p<0.002), while overexpression of these proteins caused a significant dose dependent increase in somite area (p<0.02; p<0.001, respectively). We speculate that circadian genes may play two separate roles during somitogenesis. Depletion and overexpression of xBMAL1 and NOCTURNIN both decrease somite number and influence expression of a somite clock component, suggesting that these proteins may modulate the timing of the somite clock in the undifferentiated presomitic mesoderm. The dosage dependent effects on somite area suggest that xBMAL1 and xNOCTURNIN may also act during somite differentiation to promote myogenesis.
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Curran
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Latoya
authors.initials: L
authors.lastname: Allen
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Brittany Bronson
authors.initials: BB
authors.lastname: Porter
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Dodge
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Lope
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Gail
authors.initials: G
authors.lastname: Willadsen
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: Fisher
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Nicole
authors.initials: N
authors.lastname: Johnson
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Campbell
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Brett
authors.initials: B
authors.lastname: VonBergen
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Devon
authors.initials: D
authors.lastname: Winfrey
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Morgan
authors.initials: M
authors.lastname: Hadley
authors.affiliation: University of Wisconsin-Whitewater, Department of Biological Sciences, Whitewater, Wisconsin, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kerndt
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019170:Somites / Q000166:cytology / Q000196:embryology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics*
chemical_list: D056930:ARNTL Transcription Factors; D056925:Circadian Rhythm Signaling Peptides and Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C102804:nocturnin