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Using a homozygote endogenous Her6:Venus reporter and 4D single-cell tracking, we show that Her6 oscillates in neural telencephalic progenitors and that the fusion of protein destabilisation (PEST) domain alters its expression dynamics, causing most cells to downregulate Her6 prematurely. However, counterintuitively, oscillatory cells increase, with some expressing Her6 at high levels, resulting in increased heterogeneity of Her6 expression in the population. These tissue-level changes appear to be an emergent property of coupling between single-cells, as revealed by experimentally disrupting Notch signalling and by computationally modelling alterations in Her6 protein stability. Despite the profound differences in the single-cell Her6 dynamics, the size of the telencephalon is only transiently altered and differentiation markers do not exhibit significant differences early on; however, a small increase is observed at later developmental stages. Our study suggests that cell coupling provides a compensation strategy, whereby an almost normal phenotype is maintained even though single-cell gene expression dynamics are abnormal, granting phenotypic robustness.<\/jats:p>","DOI":"10.1242\/dev.202640","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T04:32:47Z","timestamp":1714365167000},"source":"Crossref","is-referenced-by-count":10,"title":["Cell coupling compensates for changes in single-cell Her6 dynamics and provides phenotypic robustness"],"prefix":"10.1242","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4348-1196","authenticated-orcid":false,"given":"Parnian","family":"Doostdar","sequence":"first","affiliation":[{"name":"School of Medical Sciences 1 Division of Developmental Biology and Medicine , , Faculty of Biology, Medicine and Health, , Oxford Road, Manchester M13 9PT , UK"},{"name":"The University of Manchester 1 Division of Developmental Biology and Medicine , , 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