{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T21:45:24Z","timestamp":1781127924120,"version":"3.54.1"},"reference-count":83,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medical Research Council","award":["MR\/V032534\/1"],"award-info":[{"award-number":["MR\/V032534\/1"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["224394\/Z\/21\/Z"],"award-info":[{"award-number":["224394\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["201380\/Z\/16\/Z"],"award-info":[{"award-number":["201380\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["210912\/Z\/18\/Z"],"award-info":[{"award-number":["210912\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"crossref","award":["EP\/T022000\/1"],"award-info":[{"award-number":["EP\/T022000\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000770","name":"The University of Manchester","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000770","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Many cell fate decisions in the developing neural tube are directed by cross-repressive transcription factor (TF) motifs that generate bistability, such that cells express one TF but not both. Hybrid states in which cells express both cross-repressing fate determinants have been observed, but how these arise or persist remains unclear. Here, we focus on HES1 and HES5, which are auto-repressive oscillatory TFs that regulate neural progenitor maintenance and are expressed in adjacent dorsoventral progenitor domains in the developing spinal cord. Knockdown experiments demonstrate that HES1 and HES5 are cross-repressing in mouse spinal cord neural progenitors, and live-cell imaging in vitro shows that they can be co-expressed, defining a hybrid state. In this state, HES proteins co-oscillate in-phase within single cells. Computational modelling indicates that modulation of cross-repression strength or relative TF abundance destabilises this state, driving resolution towards a single oscillatory HES TF. This is consistent with in vivo analysis showing transient HES1 and HES5 co-expression, followed by progressive restriction to a single TF oscillator. Our findings suggest that oscillatory expression enables the co-existence of cross-repressing TFs, allowing hybrid states within a developmental bistable motif.<\/jats:p>","DOI":"10.1242\/dev.204969","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:29:58Z","timestamp":1777624198000},"source":"Crossref","is-referenced-by-count":1,"title":["Oscillatory co-expression of HES1 and HES5 enables a hybrid state in a cross-repressive transcription factor regulatory motif"],"prefix":"10.1242","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9592-385X","authenticated-orcid":false,"given":"Veronica","family":"Biga","sequence":"first","affiliation":[{"name":"School of Medical Sciences 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]},{"name":"The University of Manchester 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-8795","authenticated-orcid":false,"given":"Anzy","family":"Miller","sequence":"additional","affiliation":[{"name":"School of Medical Sciences 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]},{"name":"The University of Manchester 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0235-4695","authenticated-orcid":false,"given":"Anoushka","family":"Kamath","sequence":"additional","affiliation":[{"name":"School of Medical Sciences 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]},{"name":"The University of Manchester 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]},{"name":"Faculty of Biology Medicine and Health, Division of Cardiovascular Sciences 2 , University of Manchester, Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0522-3601","authenticated-orcid":false,"given":"Robert","family":"Lea","sequence":"additional","affiliation":[{"name":"School of Medical Sciences 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]},{"name":"The University of Manchester 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6260-8586","authenticated-orcid":false,"given":"Ying Q. P.","family":"Mak","sequence":"additional","affiliation":[{"name":"School of Medical Sciences 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]},{"name":"The University of Manchester 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]},{"name":"UK Dementia Research Institute 3 , University College London, London WC1E 6BT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5408-0013","authenticated-orcid":false,"given":"Antony D.","family":"Adamson","sequence":"additional","affiliation":[{"name":"Genome Editing Unit, Faculty of Biology, Medicine and Health 4 , The University of Manchester, Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6379-5168","authenticated-orcid":false,"given":"Elli","family":"Marinopoulou","sequence":"additional","affiliation":[{"name":"School of Medical Sciences 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]},{"name":"The University of Manchester 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]},{"name":"Research Development and Innovation, Faculty of Biology Medicine and Health 5 , The University of Manchester, Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2223-839X","authenticated-orcid":false,"given":"Paul","family":"Fran\u00e7ois","sequence":"additional","affiliation":[{"name":"University of Montreal 6 Department of Biochemistry and Molecular Medicine , , Montreal, Quebec QC H3T 1J4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6992-6870","authenticated-orcid":false,"given":"Nancy","family":"Papalopulu","sequence":"additional","affiliation":[{"name":"School of Medical Sciences 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]},{"name":"The University of Manchester 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8656-5878","authenticated-orcid":false,"given":"Cerys S.","family":"Manning","sequence":"additional","affiliation":[{"name":"School of Medical Sciences 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]},{"name":"The University of Manchester 1 Faculty of Biology Medicine and Health , , Division of Developmental Biology and Medicine , , Manchester M13 9PT,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"2026061012070954600_DEV204969C1","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1016\/j.stemcr.2018.04.015","article-title":"Identification and single-cell functional characterization of an endodermally biased pluripotent substate in human embryonic stem cells","volume":"10","author":"Allison","year":"2018","journal-title":"Stem Cell Rep."},{"key":"2026061012070954600_DEV204969C2","doi-asserted-by":"publisher","first-page":"e19358","DOI":"10.1371\/journal.pone.0019358","article-title":"A general model for binary cell fate decision gene circuits with degeneracy: indeterminacy and switch behavior in the absence of cooperativity","volume":"6","author":"Andrecut","year":"2011","journal-title":"PLoS ONE"},{"key":"2026061012070954600_DEV204969C3","doi-asserted-by":"publisher","first-page":"4158","DOI":"10.1242\/dev.111930","article-title":"Spatial gradients of protein-level time delays set the pace of the traveling segmentation clock waves","volume":"141","author":"Ay","year":"2014","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C4","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cell.2011.10.047","article-title":"Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube","volume":"148","author":"Balaskas","year":"2012","journal-title":"Cell"},{"key":"2026061012070954600_DEV204969C5","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.1242\/dev.147256","article-title":"Hes5 regulates the transition timing of neurogenesis and gliogenesis in mammalian neocortical development","volume":"144","author":"Bansod","year":"2017","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ymeth.2020.10.012","article-title":"CRISPR-mediated knock-in in the mouse embryo using long single stranded DNA donors synthesised by biotinylated PCR","volume":"191","author":"Bennett","year":"2021","journal-title":"Methods"},{"key":"2026061012070954600_DEV204969C7","doi-asserted-by":"publisher","first-page":"e29312","DOI":"10.7554\/eLife.29312","article-title":"Single-cell transcriptomics reveals a new dynamical function of transcription factors during embryonic hematopoiesis","volume":"7","author":"Bergiers","year":"2018","journal-title":"eLife"},{"key":"2026061012070954600_DEV204969C8","doi-asserted-by":"publisher","first-page":"e9902","DOI":"10.15252\/msb.20209902","article-title":"A dynamic, spatially periodic, micro-pattern of HES5 underlies neurogenesis in the mouse spinal cord","volume":"17","author":"Biga","year":"2021","journal-title":"Mol. Syst. Biol."},{"key":"2026061012070954600_DEV204969C9","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1093\/imammb\/dqy003","article-title":"Limit-cycle oscillatory coexpression of cross-inhibitory transcription factors: a model mechanism for lineage promiscuity","volume":"36","author":"Bokes","year":"2019","journal-title":"Math. Med. Biol."},{"key":"2026061012070954600_DEV204969C10","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1093\/imammb\/dqn026","article-title":"A bistable genetic switch which does not require high co-operativity at the promoter: a two-timescale model for the PU.1-GATA-1 interaction","volume":"26","author":"Bokes","year":"2009","journal-title":"Math. Med. Biol."},{"key":"2026061012070954600_DEV204969C11","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s11538-013-9811-z","article-title":"Transcriptional bursting diversifies the behaviour of a toggle switch: hybrid simulation of stochastic gene expression","volume":"75","author":"Bokes","year":"2013","journal-title":"Bull. Math. Biol."},{"key":"2026061012070954600_DEV204969C12","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.celrep.2012.05.017","article-title":"MicroRNA-9 modulates Hes1 ultradian oscillations by forming a double-negative feedback loop","volume":"2","author":"Bonev","year":"2012","journal-title":"Cell Rep."},{"key":"2026061012070954600_DEV204969C13","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/S0092-8674(00)80853-3","article-title":"A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube","volume":"101","author":"Briscoe","year":"2000","journal-title":"Cell"},{"key":"2026061012070954600_DEV204969C14","doi-asserted-by":"publisher","first-page":"20210393","DOI":"10.1098\/rsif.2021.0393","article-title":"Inferring kinetic parameters of oscillatory gene regulation from single cell time-series data","volume":"18","author":"Burton","year":"2021","journal-title":"J. R Soc. Interface"},{"key":"2026061012070954600_DEV204969C15","doi-asserted-by":"publisher","first-page":"dev173807","DOI":"10.1242\/dev.173807","article-title":"Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord","volume":"146","author":"Delile","year":"2019","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C16","doi-asserted-by":"publisher","first-page":"dev204583","DOI":"10.1242\/dev.204583","article-title":"Transition paths across the epithelial-mesenchymal transition landscape are dictated by network logic","volume":"152","author":"Dey","year":"2025","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C17","doi-asserted-by":"publisher","first-page":"dev202640","DOI":"10.1242\/dev.202640","article-title":"Cell coupling compensates for changes in single-cell Her6 dynamics and provides phenotypic robustness","volume":"151","author":"Doostdar","year":"2024","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C18","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1093\/bioinformatics\/btg454","article-title":"Enhancing scatterplots with smoothed densities","volume":"20","author":"Eilers","year":"2004","journal-title":"Bioinformatics"},{"key":"2026061012070954600_DEV204969C19","doi-asserted-by":"publisher","first-page":"dev202936","DOI":"10.1242\/dev.202936","article-title":"Unravelling differential Hes1 dynamics during axis elongation of mouse embryos through single-cell tracking","volume":"151","author":"El Azhar","year":"2024","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C20","doi-asserted-by":"publisher","first-page":"dev197566","DOI":"10.1242\/dev.197566","article-title":"Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks","volume":"148","author":"Exelby","year":"2021","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C21","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/S0955-0674(02)00314-9","article-title":"Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability","volume":"14","author":"Ferrell","year":"2002","journal-title":"Curr. Opin. Cell Biol."},{"key":"2026061012070954600_DEV204969C22","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.ydbio.2005.03.017","article-title":"A novel hes5\/hes6 circuitry of negative regulation controls Notch activity during neurogenesis","volume":"281","author":"Fior","year":"2005","journal-title":"Dev. Biol."},{"key":"2026061012070954600_DEV204969C23","doi-asserted-by":"publisher","first-page":"3399","DOI":"10.1038\/ncomms4399","article-title":"microRNA input into a neural ultradian oscillator controls emergence and timing of alternative cell states","volume":"5","author":"Goodfellow","year":"2014","journal-title":"Nat. Commun."},{"key":"2026061012070954600_DEV204969C83","doi-asserted-by":"publisher","first-page":"e1001937","DOI":"10.1371\/journal.pbio.1001937","article-title":"In vitro generation of neuromesodermal progenitors reveals distinct roles of Wnt signalling in the specification of spinal cord and paraxial mesoderm identity","volume":"12","author":"Gouti","year":"2014","journal-title":"PLoS Biol."},{"key":"2026061012070954600_DEV204969C24","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/S0896-6273(03)00497-5","article-title":"SOX2 functions to maintain neural progenitor identity","volume":"39","author":"Graham","year":"2003","journal-title":"Neuron"},{"key":"2026061012070954600_DEV204969C25","doi-asserted-by":"publisher","first-page":"e1000235","DOI":"10.1371\/journal.pcbi.1000235","article-title":"Multistable decision switches for flexible control of epigenetic differentiation","volume":"4","author":"Guantes","year":"2008","journal-title":"PLoS Comput. Biol."},{"key":"2026061012070954600_DEV204969C26","doi-asserted-by":"publisher","first-page":"111119","DOI":"10.1016\/j.celrep.2022.111119","article-title":"In vitro atlas of dorsal spinal interneurons reveals Wnt signaling as a critical regulator of progenitor expansion","volume":"40","author":"Gupta","year":"2022","journal-title":"Cell Rep."},{"key":"2026061012070954600_DEV204969C27","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"2026061012070954600_DEV204969C28","doi-asserted-by":"publisher","first-page":"5539","DOI":"10.1242\/dev.01436","article-title":"Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation","volume":"131","author":"Hatakeyama","year":"2004","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C29","doi-asserted-by":"publisher","first-page":"20220339","DOI":"10.1098\/rsif.2022.0339","article-title":"Dynamic switching of lateral inhibition spatial patterns","volume":"19","author":"Hawley","year":"2022","journal-title":"J. R Soc. Interface"},{"key":"2026061012070954600_DEV204969C30","doi-asserted-by":"publisher","first-page":"bio061765","DOI":"10.1242\/bio.061765","article-title":"Cellular signalling protrusions enable dynamic distant contacts in spinal cord neurogenesis","volume":"14","author":"Hawley","year":"2025","journal-title":"Biol. Open"},{"key":"2026061012070954600_DEV204969C31","doi-asserted-by":"publisher","first-page":"2596","DOI":"10.1093\/bioinformatics\/btm367","article-title":"Bayesian inference for dynamic transcriptional regulation; the Hes1 system as a case study","volume":"23","author":"Heron","year":"2007","journal-title":"Bioinformatics"},{"key":"2026061012070954600_DEV204969C32","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1126\/science.1074560","article-title":"Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop","volume":"298","author":"Hirata","year":"2002","journal-title":"Science"},{"key":"2026061012070954600_DEV204969C33","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1101\/gad.11.6.774","article-title":"Multilineage gene expression precedes commitment in the hemopoietic system","volume":"11","author":"Hu","year":"1997","journal-title":"Genes Dev."},{"key":"2026061012070954600_DEV204969C34","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1126\/science.1242366","article-title":"Oscillatory control of factors determining multipotency and fate in mouse neural progenitors","volume":"342","author":"Imayoshi","year":"2013","journal-title":"Science"},{"key":"2026061012070954600_DEV204969C35","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1242\/dev.000786","article-title":"The Hes gene family: repressors and oscillators that orchestrate embryogenesis","volume":"134","author":"Kageyama","year":"2007","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C36","doi-asserted-by":"publisher","first-page":"1254927","DOI":"10.1126\/science.1254927","article-title":"Coordination of progenitor specification and growth in mouse and chick spinal cord","volume":"345","author":"Kicheva","year":"2014","journal-title":"Science"},{"key":"2026061012070954600_DEV204969C37","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.devcel.2015.03.005","article-title":"Notch activity modulates the responsiveness of neural progenitors to sonic hedgehog signaling","volume":"33","author":"Kong","year":"2015","journal-title":"Dev. Cell"},{"key":"2026061012070954600_DEV204969C38","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.stem.2022.03.001","article-title":"Capybara: A computational tool to measure cell identity and fate transitions","volume":"29","author":"Kong","year":"2022","journal-title":"Cell Stem Cell"},{"key":"2026061012070954600_DEV204969C39","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.devcel.2016.02.013","article-title":"Neural progenitors adopt specific identities by directly repressing all alternative progenitor transcriptional programs","volume":"36","author":"Kutejova","year":"2016","journal-title":"Dev. Cell"},{"key":"2026061012070954600_DEV204969C40","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1101\/gad.322818.118","article-title":"Oscillations of MyoD and Hes1 proteins regulate the maintenance of activated muscle stem cells","volume":"33","author":"Lahmann","year":"2019","journal-title":"Genes Dev."},{"key":"2026061012070954600_DEV204969C41","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.cell.2006.06.052","article-title":"Multilineage transcriptional priming and determination of alternate hematopoietic cell fates","volume":"126","author":"Laslo","year":"2006","journal-title":"Cell"},{"key":"2026061012070954600_DEV204969C42","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1016\/S0960-9822(03)00534-7","article-title":"Autoinhibition with transcriptional delay: a simple mechanism for the zebrafish somitogenesis oscillator","volume":"13","author":"Lewis","year":"2003","journal-title":"Curr. Biol."},{"key":"2026061012070954600_DEV204969C43","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.coisb.2018.02.009","article-title":"Exploring intermediate cell states through the lens of single cells","volume":"9","author":"MacLean","year":"2018","journal-title":"Curr. Opin. Syst. Biol."},{"key":"2026061012070954600_DEV204969C44","doi-asserted-by":"publisher","first-page":"112520","DOI":"10.1016\/j.celrep.2023.112520","article-title":"Differential cell-cycle control by oscillatory versus sustained Hes1 expression via p21","volume":"42","author":"Maeda","year":"2023","journal-title":"Cell Rep."},{"key":"2026061012070954600_DEV204969C45","doi-asserted-by":"publisher","first-page":"2835","DOI":"10.1038\/s41467-019-10734-8","article-title":"Quantitative single-cell live imaging links HES5 dynamics with cell-state and fate in murine neurogenesis","volume":"10","author":"Manning","year":"2019","journal-title":"Nat. Commun."},{"key":"2026061012070954600_DEV204969C46","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/S0925-4773(98)00168-3","article-title":"Pax3 and Pax7 are expressed in commissural neurons and restrict ventral neuronal identity in the spinal cord","volume":"78","author":"Mansouri","year":"1998","journal-title":"Mech. Dev."},{"key":"2026061012070954600_DEV204969C47","doi-asserted-by":"publisher","first-page":"103198","DOI":"10.1016\/j.isci.2021.103198","article-title":"HES1 protein oscillations are necessary for neural stem cells to exit from quiescence","volume":"24","author":"Marinopoulou","year":"2021","journal-title":"iScience"},{"key":"2026061012070954600_DEV204969C48","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1016\/S0960-9822(03)00494-9","article-title":"Oscillatory expression of Hes1, p53, and NF-kappaB driven by transcriptional time delays","volume":"13","author":"Monk","year":"2003","journal-title":"Curr. Biol."},{"key":"2026061012070954600_DEV204969C49","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1016\/j.celrep.2013.04.034","article-title":"Totipotent embryonic stem cells arise in ground-state culture conditions","volume":"3","author":"Morgani","year":"2013","journal-title":"Cell Rep."},{"key":"2026061012070954600_DEV204969C50","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/nrg.2016.98","article-title":"Transition states and cell fate decisions in epigenetic landscapes","volume":"17","author":"Moris","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"2026061012070954600_DEV204969C51","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1038\/nm.1996","article-title":"Validated germline-competent embryonic stem cell lines from nonobese diabetic mice","volume":"15","author":"Nichols","year":"2009","journal-title":"Nat. Med."},{"key":"2026061012070954600_DEV204969C52","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.devcel.2007.07.013","article-title":"The initiation and propagation of Hes7 oscillation are cooperatively regulated by Fgf and notch signaling in the somite segmentation clock","volume":"13","author":"Niwa","year":"2007","journal-title":"Dev. Cell"},{"key":"2026061012070954600_DEV204969C53","doi-asserted-by":"publisher","first-page":"dev182204","DOI":"10.1242\/dev.182204","article-title":"Oscillatory expression of Hes1 regulates cell proliferation and neuronal differentiation in the embryonic brain","volume":"147","author":"Ochi","year":"2020","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C54","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/nature19348","article-title":"Single-cell analysis of mixed-lineage states leading to a binary cell fate choice","volume":"537","author":"Olsson","year":"2016","journal-title":"Nature"},{"key":"2026061012070954600_DEV204969C55","doi-asserted-by":"publisher","first-page":"e1005154","DOI":"10.1371\/journal.pcbi.1005154","article-title":"Intrinsic noise profoundly alters the dynamics and steady state of morphogen-controlled bistable genetic switches","volume":"12","author":"Perez-Carrasco","year":"2016","journal-title":"PLoS Comput. Biol."},{"key":"2026061012070954600_DEV204969C56","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.cels.2018.02.008","article-title":"Combining a toggle switch and a repressilator within the AC-DC circuit generates distinct dynamical behaviors","volume":"6","author":"Perez-Carrasco","year":"2018","journal-title":"Cell Syst."},{"key":"2026061012070954600_DEV204969C57","doi-asserted-by":"publisher","first-page":"e1005479","DOI":"10.1371\/journal.pcbi.1005479","article-title":"Identifying stochastic oscillations in single-cell live imaging time series using Gaussian processes","volume":"13","author":"Phillips","year":"2017","journal-title":"PLoS Comput. Biol."},{"key":"2026061012070954600_DEV204969C58","doi-asserted-by":"publisher","first-page":"3081","DOI":"10.1242\/dev.021519","article-title":"Distinct sequential cell behaviours direct primitive endoderm formation in the mouse blastocyst","volume":"135","author":"Plusa","year":"2008","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C59","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/978-1-62703-574-3_2","article-title":"In vitro expansion of fetal neural progenitors as adherent cell lines","volume":"1059","author":"Pollard","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"2026061012070954600_DEV204969C60","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s13059-017-1220-4","article-title":"Easi-CRISPR: a robust method for one-step generation of mice carrying conditional and insertion alleles using long ssDNA donors and CRISPR ribonucleoproteins","volume":"18","author":"Quadros","year":"2017","journal-title":"Genome Biol."},{"key":"2026061012070954600_DEV204969C61","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.stemcr.2023.12.002","article-title":"Transcription factor co-expression mediates lineage priming for embryonic and extra-embryonic differentiation","volume":"19","author":"Redo-Riveiro","year":"2024","journal-title":"Stem Cell Rep."},{"key":"2026061012070954600_DEV204969C62","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1002\/dvdy.24542","article-title":"Separate and coincident expression of Hes1 and Hes5 in the developing mouse eye","volume":"247","author":"Riesenberg","year":"2018","journal-title":"Dev. Dyn."},{"key":"2026061012070954600_DEV204969C63","doi-asserted-by":"publisher","first-page":"063114","DOI":"10.1063\/1.5018262","article-title":"Bistability in two simple symmetrically coupled oscillators with symmetry-broken amplitude- and phase-locking","volume":"28","author":"Rohm","year":"2018","journal-title":"Chaos"},{"key":"2026061012070954600_DEV204969C64","doi-asserted-by":"publisher","first-page":"e1008231","DOI":"10.1371\/journal.pcbi.1008231","article-title":"Dynamic bistable switches enhance robustness and accuracy of cell cycle transitions","volume":"17","author":"Rombouts","year":"2021","journal-title":"PLoS Comput. Biol."},{"key":"2026061012070954600_DEV204969C65","doi-asserted-by":"publisher","first-page":"dev182154","DOI":"10.1242\/dev.182154","article-title":"Establishing neuronal diversity in the spinal cord: a time and a place","volume":"146","author":"Sagner","year":"2019","journal-title":"Development"},{"key":"2026061012070954600_DEV204969C66","doi-asserted-by":"publisher","first-page":"e2003127","DOI":"10.1371\/journal.pbio.2003127","article-title":"Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics","volume":"16","author":"Sagner","year":"2018","journal-title":"PLoS Biol."},{"key":"2026061012070954600_DEV204969C67","doi-asserted-by":"publisher","first-page":"e79575","DOI":"10.7554\/eLife.79575","article-title":"Arnold tongue entrainment reveals dynamical principles of the embryonic segmentation clock","volume":"11","author":"Sanchez","year":"2022","journal-title":"eLife"},{"key":"2026061012070954600_DEV204969C68","doi-asserted-by":"publisher","first-page":"e1001364","DOI":"10.1371\/journal.pbio.1001364","article-title":"Topology and dynamics of the zebrafish segmentation clock core circuit","volume":"10","author":"Schr\u00f6ter","year":"2012","journal-title":"PLoS Biol."},{"key":"2026061012070954600_DEV204969C69","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.devcel.2020.01.015","article-title":"Jag1 modulates an oscillatory Dll1-Notch-Hes1 signaling module to coordinate growth and fate of pancreatic progenitors","volume":"52","author":"Seymour","year":"2020","journal-title":"Dev. Cell"},{"key":"2026061012070954600_DEV204969C70","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1101\/gad.270785.115","article-title":"Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis","volume":"30","author":"Shimojo","year":"2016","journal-title":"Genes Dev."},{"key":"2026061012070954600_DEV204969C71","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1016\/j.devcel.2024.04.019","article-title":"The Neurog2-Tbr2 axis forms a continuous transition to the neurogenic gene expression state in neural stem cells","volume":"59","author":"Shimojo","year":"2024","journal-title":"Dev. Cell"},{"key":"2026061012070954600_DEV204969C72","doi-asserted-by":"publisher","first-page":"e103558","DOI":"10.15252\/embj.2019103558","article-title":"Dynamic properties of noise and Her6 levels are optimized by miR-9, allowing the decoding of the Her6 oscillator","volume":"39","author":"Soto","year":"2020","journal-title":"EMBO J."},{"key":"2026061012070954600_DEV204969C73","doi-asserted-by":"publisher","first-page":"4989","DOI":"10.1038\/s41467-020-18727-8","article-title":"Generation and trapping of a mesoderm biased state of human pluripotency","volume":"11","author":"Stavish","year":"2020","journal-title":"Nat. Commun."},{"key":"2026061012070954600_DEV204969C74","doi-asserted-by":"publisher","first-page":"5150","DOI":"10.1016\/S0021-9258(17)37668-8","article-title":"Structure, chromosomal locus, and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation through the multiple N box elements","volume":"269","author":"Takebayashi","year":"1994","journal-title":"J. Biol. Chem."},{"key":"2026061012070954600_DEV204969C75","doi-asserted-by":"publisher","first-page":"120179","DOI":"10.1098\/rsob.120179","article-title":"Molecular mechanisms creating bistable switches at cell cycle transitions","volume":"3","author":"Verdugo","year":"2013","journal-title":"Open Biol."},{"key":"2026061012070954600_DEV204969C76","doi-asserted-by":"publisher","first-page":"6638","DOI":"10.1073\/pnas.0806137106","article-title":"Bistable switches control memory and plasticity in cellular differentiation","volume":"106","author":"Wang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026061012070954600_DEV204969C77","doi-asserted-by":"publisher","first-page":"e23702","DOI":"10.7554\/eLife.23702","article-title":"Engineering of a synthetic quadrastable gene network to approach Waddington landscape and cell fate determination","volume":"6","author":"Wu","year":"2017","journal-title":"eLife"},{"key":"2026061012070954600_DEV204969C78","doi-asserted-by":"publisher","first-page":"3145","DOI":"10.1038\/s41467-021-23425-0","article-title":"Yeast cell fate control by temporal redundancy modulation of transcription factor paralogs","volume":"12","author":"Wu","year":"2021","journal-title":"Nat. Commun."},{"key":"2026061012070954600_DEV204969C79","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nature06968","article-title":"The ground state of embryonic stem cell self-renewal","volume":"453","author":"Ying","year":"2008","journal-title":"Nature"},{"key":"2026061012070954600_DEV204969C80","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/nature06878","article-title":"TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function","volume":"453","author":"Zhou","year":"2008","journal-title":"Nature"},{"key":"2026061012070954600_DEV204969C81","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.jtbi.2007.01.021","article-title":"Studying genetic regulatory networks at the molecular level: delayed reaction stochastic models","volume":"246","author":"Zhu","year":"2007","journal-title":"J. Theor. Biol."},{"key":"2026061012070954600_DEV204969C82","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.coisb.2020.12.002","article-title":"Synthetic designs regulating cellular transitions: fine-tuning of switches and oscillators","volume":"25","author":"Zorzan","year":"2021","journal-title":"Curr. Opin. Syst. Biol."}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.204969\/3697373\/dev204969.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.204969\/3703184\/dev204969.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.204969\/3703184\/dev204969.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:07:22Z","timestamp":1781107642000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/153\/11\/dev204969\/371928\/Oscillatory-co-expression-of-HES1-and-HES5-enables"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":83,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.204969","relation":{},"ISSN":["0950-1991","1477-9129"],"issn-type":[{"value":"0950-1991","type":"print"},{"value":"1477-9129","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,1]]},"article-number":"dev204969"}}