Suprachiasmatic nucleus grafts restore circadian behavioral rhythms of genetically arrhythmic mice.
The mammalian master clock driving circadian rhythmicity in physiology and behavior resides within the suprachiasmatic nuclei (SCN) of the hypothalamus. SCN neurons contain a molecular oscillator composed of a set of clock genes that acts in intertwined negative and positive feedback loops [1]. In addition, all peripheral tissues analyzed thus far have been shown to contain circadian oscillators [2]. This raises the question of whether the central circadian pacemaker in the SCN is sufficient to evoke behavioral rhythms or whether peripheral circadian clockworks are also required. Mice with a mutated CLOCK protein (a transcriptional activator of E box-containing clock and clock output genes) or lacking both CRYPTOCHROMES, mCRY1 and mCRY2 proteins (inhibitors of E box-mediated transcription), lack circadian rhythmicity in behavior [3,4]. Here, we show that transplantation of mouse fetal SCN tissue into the hypothalamus restores free-running circadian behavioral rhythmicity in Clock mutant or mCry1/mCry2 double knockout mice. The periodicity of the emerged rhythms is determined by the genetic constitution (i.e., wild-type or mCry2 knockout) of the grafted SCN. Since transplanted mCry1/mCry2-deficient mice do not have functional circadian oscillators [5] other than those present in the grafted hypothalamus region, these findings suggest that the SCN can generate circadian behavioral rhythms in the absence of distant peripheral oscillators in the brain or elsewhere.
Sujino
Mitsugu
M
Department of Physics, Informatics, and Biology, Yamaguchi University, Yoshida, Yamaguchi 753-8512, Japan.
Masumoto
Koh-hei
KH
Yamaguchi
Shun
S
van der Horst
Gijsbertus T J
GT
Okamura
Hitoshi
H
Inouye
Shin-Ichi T
ST
D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology*; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins / Q000235:genetics; D007031:Hypothalamus / Q000033:anatomy & histology; D007150:Immunohistochemistry; D008124:Locomotion / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D017956:Photoreceptor Cells, Invertebrate; D043562:Receptors, G-Protein-Coupled; D013493:Suprachiasmatic Nucleus / Q000502:physiology* / Q000637:transplantation*; D015534:Trans-Activators / Q000235:genetics
D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators; C119828:cry protein, Drosophila; D056926:CLOCK Proteins; C538944:Clock protein, mouse