Journal
EMBO JOURNAL
Volume 40, Issue 20, Pages -Publisher
WILEY
DOI: 10.15252/embj.2021108614
Keywords
neural network; neuropeptides; Prokineticin receptor 2; Prokineticin2; single-cell transcriptomics
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Funding
- UK Medical Research Council UK [MC_U105170643]
- Biotechnology and Biological Sciences Research Council [BB/R016658/1]
- BBSRC [BB/R016658/1] Funding Source: UKRI
- MRC [MC_U105170643] Funding Source: UKRI
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The study reveals the diverse and distinct contributions of neuropeptide-modulated communication of temporal information across the SCN. By investigating the Prok2-ProkR2 neuropeptidergic axis, it is shown to play a key regulatory role in SCN period and rhythmicity, contributing to defining the network-level properties that underpin robust circadian co-ordination.
Circadian rhythms in mammals are governed by the hypothalamic suprachiasmatic nucleus (SCN), in which 20,000 clock cells are connected together into a powerful time-keeping network. In the absence of network-level cellular interactions, the SCN fails as a clock. The topology and specific roles of its distinct cell populations (nodes) that direct network functions are, however, not understood. To characterise its component cells and network structure, we conducted single-cell sequencing of SCN organotypic slices and identified eleven distinct neuronal sub-populations across circadian day and night. We defined neuropeptidergic signalling axes between these nodes, and built neuropeptide-specific network topologies. This revealed their temporal plasticity, being up-regulated in circadian day. Through intersectional genetics and real-time imaging, we interrogated the contribution of the Prok2-ProkR2 neuropeptidergic axis to network-wide time-keeping. We showed that Prok2-ProkR2 signalling acts as a key regulator of SCN period and rhythmicity and contributes to defining the network-level properties that underpin robust circadian co-ordination. These results highlight the diverse and distinct contributions of neuropeptide-modulated communication of temporal information across the SCN.
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