First Author | Morris EL | Year | 2021 |
Journal | EMBO J | Volume | 40 |
Issue | 20 | Pages | e108614 |
PubMed ID | 34487375 | Mgi Jnum | J:350344 |
Mgi Id | MGI:6790024 | Doi | 10.15252/embj.2021108614 |
Citation | Morris EL, et al. (2021) Single-cell transcriptomics of suprachiasmatic nuclei reveal a Prokineticin-driven circadian network. EMBO J 40(20):e108614 |
abstractText | 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. |