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dc.contributor.authorSoto, Ximena
dc.contributor.authorBurton, Joshua
dc.contributor.authorManning, Cerys S.
dc.contributor.authorMinchington, Thomas
dc.contributor.authorLea, Robert
dc.contributor.authorLee, Jessica
dc.contributor.authorKursawe, Jochen
dc.contributor.authorRattray, Magnus
dc.contributor.authorPapalopulu, Nancy
dc.identifier.citationSoto , X , Burton , J , Manning , C S , Minchington , T , Lea , R , Lee , J , Kursawe , J , Rattray , M & Papalopulu , N 2022 , ' Sequential and additive expression of miR-9 precursors control timing of neurogenesis ' , Development , vol. 149 , no. 19 , dev200474 .
dc.identifier.otherPURE: 281864590
dc.identifier.otherPURE UUID: d73ad32a-0c82-4b29-8054-3254b062c517
dc.identifier.otherJisc: 637442
dc.identifier.otherpublisher-id: dev200474
dc.identifier.otherScopus: 85139100943
dc.identifier.otherORCID: /0000-0002-0314-9623/work/121753850
dc.descriptionThis work was supported by a Wellcome Trust Senior Research Fellowship (090868/Z/09/Z) and a Wellcome Trust Investigator Award (224394/Z/21/Z) to N.P. and a Medical Research Council Career Development Award to C.S.M. (MR/V032534/1). J.B. was supported by a Wellcome Trust Four-Year PhD Studentship in Basic Science (219992/Z/19/Z). Open Access funding provided by The University of Manchester.en
dc.description.abstractMicroRNAs (miRs) have an important role in tuning dynamic gene expression. However, the mechanism by which they are quantitatively controlled is unknown. We show that the amount of mature miR-9, a key regulator of neuronal development, increases during zebrafish neurogenesis in a sharp stepwise manner. We characterize the spatiotemporal profile of seven distinct microRNA primary transcripts (pri-mir)-9s that produce the same mature miR-9 and show that they are sequentially expressed during hindbrain neurogenesis. Expression of late-onset pri-mir-9-1 is added on to, rather than replacing, the expression of early onset pri-mir-9-4 and -9-5 in single cells. CRISPR/Cas9 mutation of the late-onset pri-mir-9-1 prevents the developmental increase of mature miR-9, reduces late neuronal differentiation and fails to downregulate Her6 at late stages. Mathematical modelling shows that an adaptive network containing Her6 is insensitive to linear increases in miR-9 but responds to stepwise increases of miR-9. We suggest that a sharp stepwise increase of mature miR-9 is created by sequential and additive temporal activation of distinct loci. This may be a strategy to overcome adaptation and facilitate a transition of Her6 to a new dynamic regime or steady state.
dc.rightsCopyright © 2022 Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.en
dc.subjectTemporal controlen
dc.subjectQH301 Biologyen
dc.titleSequential and additive expression of miR-9 precursors control timing of neurogenesisen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. Statisticsen
dc.contributor.institutionUniversity of St Andrews. Applied Mathematicsen
dc.description.statusPeer revieweden

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