Spatial Patterning from an Integrated Wnt/β-catenin and Notch/Delta Gene Circuit.

Published

Journal Article

Classically, the Wnt/β-catenin and Notch /Delta signaling pathways were thought to operate through separate mechanisms, performing distinct roles in tissue patterning. However, it has been shown that b-catenin activates transcription of Hesl, a signaling intermediate in the Notch /Delta pathway that controls its lateral inhibition mechanism. To investigate this non-canonical crosstalk mechanism, a new gene circuit, integrating the two pathways, is proposed and simulated in two-cell and multi-cell environments. This model also captures both Paneth cell- mediated and mesenchymal Wnt production. The simulations verify that the gene circuit is temporally bistable and capable of forming a pattern on a multi-cell grid. Last, the model exhibits a bifurcation based on the steady state concentration of Wnt and the relative amount of control b-catenin has over the Hesl promoter, providing a possible mechanism to explain why a homogeneous population of transit amplifying cells is observed directly above the more diverse stem niche.

Full Text

Duke Authors

Cited Authors

  • Mines, RC; Dohlman, A; Lim, S-X; Tung, K-L; Wang, E; Shen, X

Published Date

  • July 2018

Published In

Volume / Issue

  • 2018 /

Start / End Page

  • 5022 - 5025

PubMed ID

  • 30441469

Pubmed Central ID

  • 30441469

International Standard Serial Number (ISSN)

  • 1557-170X

Digital Object Identifier (DOI)

  • 10.1109/embc.2018.8513462

Language

  • eng