TY - JOUR
T1 - Dynamic switching of lateral inhibition spatial patterns
AU - Hawley, Joshua
AU - Manning, Cerys
AU - Biga, Veronica
AU - Glendinning, Paul
AU - Papalopulu, Nancy
N1 - Publisher Copyright:
© 2022 The Authors.
PY - 2022/8/24
Y1 - 2022/8/24
N2 - Hes genes are transcriptional repressors activated by Notch. In the developing mouse neural tissue, HES5 expression oscillates in neural progenitors (Manning et al. 2019 Nat. Commun. 10, 1-19 (doi:10.1038/s41467-019-10734-8)) and is spatially organized in small clusters of cells with synchronized expression (microclusters). Furthermore, these microclusters are arranged with a spatial periodicity of three-four cells in the dorso-ventral axis and show regular switching between HES5 high/low expression on a longer time scale and larger amplitude than individual temporal oscillators (Biga et al. 2021 Mol. Syst. Biol. 17, e9902 (doi:10.15252/msb.20209902)). However, our initial computational modelling of coupled HES5 could not explain these features of the experimental data. In this study, we provide theoretical results that address these issues with biologically pertinent additions. Here, we report that extending Notch signalling to non-neighbouring progenitor cells is sufficient to generate spatial periodicity of the correct size. In addition, introducing a regular perturbation of Notch signalling by the emerging differentiating cells induces a temporal switching in the spatial pattern, which is longer than an individual cell's periodicity. Thus, with these two new mechanisms, a computational model delivers outputs that closely resemble the complex tissue-level HES5 dynamics. Finally, we predict that such dynamic patterning spreads out differentiation events in space, complementing our previous findings whereby the local synchronization controls the rate of differentiation.
AB - Hes genes are transcriptional repressors activated by Notch. In the developing mouse neural tissue, HES5 expression oscillates in neural progenitors (Manning et al. 2019 Nat. Commun. 10, 1-19 (doi:10.1038/s41467-019-10734-8)) and is spatially organized in small clusters of cells with synchronized expression (microclusters). Furthermore, these microclusters are arranged with a spatial periodicity of three-four cells in the dorso-ventral axis and show regular switching between HES5 high/low expression on a longer time scale and larger amplitude than individual temporal oscillators (Biga et al. 2021 Mol. Syst. Biol. 17, e9902 (doi:10.15252/msb.20209902)). However, our initial computational modelling of coupled HES5 could not explain these features of the experimental data. In this study, we provide theoretical results that address these issues with biologically pertinent additions. Here, we report that extending Notch signalling to non-neighbouring progenitor cells is sufficient to generate spatial periodicity of the correct size. In addition, introducing a regular perturbation of Notch signalling by the emerging differentiating cells induces a temporal switching in the spatial pattern, which is longer than an individual cell's periodicity. Thus, with these two new mechanisms, a computational model delivers outputs that closely resemble the complex tissue-level HES5 dynamics. Finally, we predict that such dynamic patterning spreads out differentiation events in space, complementing our previous findings whereby the local synchronization controls the rate of differentiation.
KW - HES5
KW - notch signalling
KW - dynamic switching
KW - lateral inhibition
KW - neural tube
KW - spatial pattern
UR - http://www.scopus.com/inward/record.url?scp=85136428610&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/e9cb383b-53ef-300a-b0ac-ce5414635628/
U2 - 10.1098/rsif.2022.0339
DO - 10.1098/rsif.2022.0339
M3 - Article
C2 - 36000231
SN - 1742-5689
VL - 19
SP - 1
EP - 17
JO - Journal of the Royal Society Interface
JF - Journal of the Royal Society Interface
IS - 193
M1 - 20220339
ER -