Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Syst Biol
2021 May 01;175:e9902. doi: 10.15252/msb.20209902.
Show Gene links
Show Anatomy links
A dynamic, spatially periodic, micro-pattern of HES5 underlies neurogenesis in the mouse spinal cord.
Biga V
,
Hawley J
,
Soto X
,
Johns E
,
Han D
,
Bennett H
,
Adamson AD
,
Kursawe J
,
Glendinning P
,
Manning CS
,
Papalopulu N
.
???displayArticle.abstract???
Ultradian oscillations of HES Transcription Factors (TFs) at the single-cell level enable cell state transitions. However, the tissue-level organisation of HES5 dynamics in neurogenesis is unknown. Here, we analyse the expression of HES5 ex vivo in the developing mouse ventral spinal cord and identify microclusters of 4-6 cells with positively correlated HES5 level and ultradian dynamics. These microclusters are spatially periodic along the dorsoventral axis and temporally dynamic, alternating between high and low expression with a supra-ultradian persistence time. We show that Notch signalling is required for temporal dynamics but not the spatial periodicity of HES5. Few Neurogenin 2 cells are observed per cluster, irrespective of high or low state, suggesting that the microcluster organisation of HES5 enables the stable selection of differentiating cells. Computational modelling predicts that different cell coupling strengths underlie the HES5 spatial patterns and rate of differentiation, which is consistent with comparison between the motoneuron and interneuron progenitor domains. Our work shows a previously unrecognised spatiotemporal organisation of neurogenesis, emergent at the tissue level from the synthesis of single-cell dynamics.
Baek,
Mib1 prevents Notch Cis-inhibition to defer differentiation and preserve neuroepithelial integrity during neural delamination.
2018, Pubmed
Baek,
Mib1 prevents Notch Cis-inhibition to defer differentiation and preserve neuroepithelial integrity during neural delamination.
2018,
Pubmed
Bansod,
Hes5 regulates the transition timing of neurogenesis and gliogenesis in mammalian neocortical development.
2017,
Pubmed
Baron,
Intrinsic noise, Delta-Notch signalling and delayed reactions promote sustained, coherent, synchronized oscillations in the presomitic mesoderm.
2019,
Pubmed
Boareto,
Jagged-Delta asymmetry in Notch signaling can give rise to a Sender/Receiver hybrid phenotype.
2015,
Pubmed
Bonev,
MicroRNA-9 Modulates Hes1 ultradian oscillations by forming a double-negative feedback loop.
2012,
Pubmed
,
Xenbase
Briscoe,
Morphogen rules: design principles of gradient-mediated embryo patterning.
2015,
Pubmed
Choi,
Synchronization in a system of globally coupled oscillators with time delay.
2000,
Pubmed
Cohen,
Dynamic filopodia transmit intermittent Delta-Notch signaling to drive pattern refinement during lateral inhibition.
2010,
Pubmed
Corson,
Self-organized Notch dynamics generate stereotyped sensory organ patterns in Drosophila.
2017,
Pubmed
Das,
Mitotic spindle orientation can direct cell fate and bias Notch activity in chick neural tube.
2012,
Pubmed
Das,
Apical abscission alters cell polarity and dismantles the primary cilium during neurogenesis.
2014,
Pubmed
De Joussineau,
Delta-promoted filopodia mediate long-range lateral inhibition in Drosophila.
2003,
Pubmed
Delile,
Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord.
2019,
Pubmed
Eilers,
Enhancing scatterplots with smoothed densities.
2004,
Pubmed
Falo-Sanjuan,
Decoding the Notch signal.
2020,
Pubmed
Galla,
Intrinsic fluctuations in stochastic delay systems: theoretical description and application to a simple model of gene regulation.
2009,
Pubmed
Goodfellow,
microRNA input into a neural ultradian oscillator controls emergence and timing of alternative cell states.
2014,
Pubmed
,
Xenbase
Hadjivasiliou,
Basal Protrusions Mediate Spatiotemporal Patterns of Spinal Neuron Differentiation.
2019,
Pubmed
Henrique,
Mechanisms of Notch signaling: a simple logic deployed in time and space.
2019,
Pubmed
Herrgen,
Intercellular coupling regulates the period of the segmentation clock.
2010,
Pubmed
Hunter,
Coordinated control of Notch/Delta signalling and cell cycle progression drives lateral inhibition-mediated tissue patterning.
2016,
Pubmed
Imayoshi,
Oscillatory control of factors determining multipotency and fate in mouse neural progenitors.
2013,
Pubmed
Imayoshi,
bHLH factors in self-renewal, multipotency, and fate choice of neural progenitor cells.
2014,
Pubmed
Isomura,
Optogenetic perturbation and bioluminescence imaging to analyze cell-to-cell transfer of oscillatory information.
2017,
Pubmed
Jensen,
Sustained oscillations and time delays in gene expression of protein Hes1.
2003,
Pubmed
Kageyama,
Dynamic Notch signaling in neural progenitor cells and a revised view of lateral inhibition.
2008,
Pubmed
Kicheva,
Coordination of progenitor specification and growth in mouse and chick spinal cord.
2014,
Pubmed
Kobayashi,
The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.
2009,
Pubmed
Kuzmicz-Kowalska,
Regulation of size and scale in vertebrate spinal cord development.
2021,
Pubmed
Lewis,
Autoinhibition with transcriptional delay: a simple mechanism for the zebrafish somitogenesis oscillator.
2003,
Pubmed
Lopes-Dos-Santos,
Parsing Hippocampal Theta Oscillations by Nested Spectral Components during Spatial Exploration and Memory-Guided Behavior.
2018,
Pubmed
Lyubimova,
Single-molecule mRNA detection and counting in mammalian tissue.
2013,
Pubmed
Ma,
neurogenin1 is essential for the determination of neuronal precursors for proximal cranial sensory ganglia.
1998,
Pubmed
,
Xenbase
Manning,
Quantitative single-cell live imaging links HES5 dynamics with cell-state and fate in murine neurogenesis.
2019,
Pubmed
Marklund,
Domain-specific control of neurogenesis achieved through patterned regulation of Notch ligand expression.
2010,
Pubmed
Marra,
Prostaglandin signaling regulates renal multiciliated cell specification and maturation.
2019,
Pubmed
Momiji,
Dissecting the dynamics of the Hes1 genetic oscillator.
2008,
Pubmed
Monk,
Oscillatory expression of Hes1, p53, and NF-kappaB driven by transcriptional time delays.
2003,
Pubmed
Morelli,
Delayed coupling theory of vertebrate segmentation.
2009,
Pubmed
Nelson,
Intermediate progenitors support migration of neural stem cells into dentate gyrus outer neurogenic niches.
2020,
Pubmed
Oates,
Waiting on the Fringe: cell autonomy and signaling delays in segmentation clocks.
2020,
Pubmed
Ohtsuka,
Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation.
1999,
Pubmed
Ozbudak,
Notch signalling synchronizes the zebrafish segmentation clock but is not needed to create somite boundaries.
2008,
Pubmed
Paridaen,
Neurogenesis during development of the vertebrate central nervous system.
2014,
Pubmed
Petrovic,
Ligand-dependent Notch signaling strength orchestrates lateral induction and lateral inhibition in the developing inner ear.
2014,
Pubmed
Phillips,
Stochasticity in the miR-9/Hes1 oscillatory network can account for clonal heterogeneity in the timing of differentiation.
2016,
Pubmed
,
Xenbase
Ramos,
Two Notch ligands, Dll1 and Jag1, are differently restricted in their range of action to control neurogenesis in the mammalian spinal cord.
2010,
Pubmed
Sagner,
Establishing neuronal diversity in the spinal cord: a time and a place.
2019,
Pubmed
Sagner,
Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics.
2018,
Pubmed
Shaya,
From Notch signaling to fine-grained patterning: Modeling meets experiments.
2011,
Pubmed
Shimojo,
Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis.
2016,
Pubmed
Shimojo,
Oscillatory control of Delta-like1 in somitogenesis and neurogenesis: A unified model for different oscillatory dynamics.
2016,
Pubmed
Sonnen,
Modulation of Phase Shift between Wnt and Notch Signaling Oscillations Controls Mesoderm Segmentation.
2018,
Pubmed
Soto,
Dynamic properties of noise and Her6 levels are optimized by miR-9, allowing the decoding of the Her6 oscillator.
2020,
Pubmed
,
Xenbase
Sprinzak,
Cis-interactions between Notch and Delta generate mutually exclusive signalling states.
2010,
Pubmed
Tiedemann,
Modeling coexistence of oscillation and Delta/Notch-mediated lateral inhibition in pancreas development and neurogenesis.
2017,
Pubmed
Tsiairis,
Self-Organization of Embryonic Genetic Oscillators into Spatiotemporal Wave Patterns.
2016,
Pubmed
Vilas-Boas,
A novel reporter of notch signalling indicates regulated and random Notch activation during vertebrate neurogenesis.
2011,
Pubmed
Webb,
Persistence, period and precision of autonomous cellular oscillators from the zebrafish segmentation clock.
2016,
Pubmed
Wu,
Ultradian calcium rhythms in the paraventricular nucleus and subparaventricular zone in the hypothalamus.
2018,
Pubmed