English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The Notch pathway plays a vital role in determining whether cells in theintestinal epithelium adopt a secretory or an absorptive phenotype. Cell fatespecification is coordinated via Notch's interaction with the canonical Wntpathway. Here, we propose a new mathematical model of the Notch and Wntpathways, in which the Hes1 promoter acts as a hub for pathway crosstalk.Computational simulations of the model can assist in understanding how healthyintestinal tissue is maintained, and predict the likely consequences ofbiochemical knockouts upon cell fate selection processes. Chemical reactionnetwork theory (CRNT) is a powerful, generalised framework which assesses thecapacity of our model for monostability or multistability, by analysingproperties of the underlying network structure without recourse to specificparameter values or functional forms for reaction rates. CRNT highlights therole of beta-catenin in stabilising the Notch pathway and damping oscillations,demonstrating that Wnt-mediated actions on the Hes1 promoter can inducedynamical transitions in the Notch system, from multistability tomonostability. Time-dependent model simulations of cell pairs reveal thestabilising influence of Wnt upon the Notch pathway, in which beta-catenin- andDsh-mediated action on the Hes1 promoter are key in shaping the subcellulardynamics. Where Notch-mediated transcription of Hes1 dominates, there is Notchoscillation and maintenance of fate flexibility; Wnt-mediated transcription ofHes1 favours bistability akin to cell fate selection. Cells could thereforeregulate the proportion of Wnt- and Notch-mediated control of the Hes1 promoterto coordinate the timing of cell fate selection as they migrate through theintestinal epithelium and are subject to reduced Wnt stimuli.

The Role of the Hes1 Crosstalk Hub in Notch-Wnt Interactions of the Intestinal Crypt