The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits
Open accessAbstract
The suprachiasmatic nucleus (SCN) is the principal circadian pacemaker of mammals, coordinating daily rhythms of behavior and metabolism. Circadian timekeeping in SCN neurons revolves around transcriptional/posttranslational feedback loops, in which Period ( Per ) and Cryptochrome ( Cry ) genes are negatively regulated by their protein products. Recent studies have revealed, however, that these “core loops” also rely upon cytosolic and circuit-level properties for sustained oscillation. To characterize interneuronal signals responsible for robust pacemaking in SCN cells and circuits, we have developed a unique coculture technique using wild-type (WT) “graft” SCN to drive pacemaking (reported by PER2::LUCIFERASE bioluminescence) in “host” SCN deficient either in elements of neuropeptidergic signaling or in elements of the core feedback loop. We demonstrate that paracrine signaling is sufficient to restore cellular synchrony and amplitude of pacemaking in SCN circuits lacking vasoactive intestinal peptide (VIP). By using grafts with mutant circadian periods we show that pacemaking in the host SCN is specified by the genotype of the graft, confirming graft-derived factors as determinants of the host rhythm. By combining pharmacological with genetic manipulations, we show that a hierarchy of neuropeptidergic signals underpins this paracrine regulation, with a preeminent role for VIP augmented by contributions from arginine vasopressin (AVP) and gastrin-releasing peptide (GRP). Finally, we show that interneuronal signaling is sufficiently powerful to maintain circadian pacemaking in arrhythmic Cry-null SCN, deficient in essential elements of the transcriptional negative feedback loops. Thus, a hierarchy of paracrine neuropeptidergic signals determines cell- and circuit-level circadian pacemaking in the SCN.
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Cites
mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop
Kume, K., Zylka, M. J., Sriram, S., Shearman, L. P., Weaver, D. R., Jin, X., Maywood, E. S., Hastings, M. H., & Reppert, S. M. (1999) · Cell · doi:10.1016/s0092-8674(00)81014-4 · Cited by 1,617
Self-citationThe genetics of mammalian circadian order and disorder: implications for physiology and disease
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Suprachiasmatic Nucleus: Cell Autonomy and Network Properties
Welsh, D. K., Takahashi, J. S., & Kay, S. A. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135919 · Cited by 1,216
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Intercellular Coupling Confers Robustness against Mutations in the SCN Circadian Clock Network
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Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis
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The VPAC2 Receptor Is Essential for Circadian Function in the Mouse Suprachiasmatic Nuclei
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Self-citationThe After-Hours Mutant Reveals a Role for Fbxl3 in Determining Mammalian Circadian Period
Godinho, S. I. H., Maywood, E. S., Shaw, L., Tucci, V., Barnard, A. R., Busino, L., Pagano, M., Kendall, R., Quwailid, M. M., Romero, M. R., et al. (2007) · Science · doi:10.1126/science.1141138 · Cited by 475
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Cited by
Generation of circadian rhythms in the suprachiasmatic nucleus
Hastings, M. H., Maywood, E. S., & Brancaccio, M. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0026-z · Cited by 1,065
Self-citationNeural Circuitry of Wakefulness and Sleep
Scammell, T. E., Arrigoni, E., & Lipton, J. O. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.014 · Cited by 966
Linking neural activity and molecular oscillations in the SCN
Colwell, C. S. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3086 · Cited by 474
Astrocytes Control Circadian Timekeeping in the Suprachiasmatic Nucleus via Glutamatergic Signaling
Brancaccio, M., Patton, A. P., Chesham, J. E., Maywood, E. S., & Hastings, M. H. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.030 · Cited by 434
Self-citationMedicine in the Fourth Dimension
Cederroth, C. R., Albrecht, U., Bass, J., Brown, S. A., Dyhrfjeld-Johnsen, J., Gachon, F., Green, C. B., Hastings, M. H., Helfrich-Förster, C., Hogenesch, J. B., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.06.019 · Cited by 359
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Metadata
- Authors
- Maywood, E. S., Chesham, J. E., O'Brien, J. A., & Hastings, M. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-07-25
- Volume
- 108
- Issue
- 34
- Pages
- 14306-14311
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2170167067
- Cited by
- 287
- References
- 37
- FWCI
- 8.33
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Maywood, E. S., Chesham, J. E., O'Brien, J. A., & Hastings, M. H. (2011). A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1101767108
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