4.7 Article

Robust boundary formation in a morphogen gradient via cell-cell signaling

Journal

PHYSICAL REVIEW E
Volume 105, Issue 6, Pages -

Publisher

AMER PHYSICAL SOC
DOI: 10.1103/PhysRevE.105.064405

Keywords

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Funding

  1. German Research Foundation [SFB1032]
  2. DFG fellowship through the Graduate School of Quantitative Biosciences Munich (QBM)

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This research explores enhancing boundary formation processes by combining global morphogen gradient signals with local signaling between neighboring cells in the presence of noise. Three mechanisms were analyzed, with the SUM rule mechanism producing the most accurate boundaries compared to the other two mechanisms.
Establishing sharp and correctly positioned boundaries in spatial gene expression patterns is a central task in both developmental and synthetic biology. We consider situations where a global morphogen gradient provides positional information to cells but is insufficient to ensure the required boundary precision, due to different types of noise in the system. In a conceptual model, we quantitatively compare three mechanisms, which combine the global signal with local signaling between neighboring cells, to enhance the boundary formation process. These mechanisms differ with respect to the way in which they combine the signals by following either an AND, an OR, or a SUM rule. Within our model, we analyze the dynamics of the boundary formation process, and the fuzziness of the resulting boundary. Furthermore, we consider the tunability of the boundary position and its scaling with system size. We find that all three mechanisms produce less fuzzy boundaries than the purely gradient-based reference mechanism, even in the regime of high noise in the local signals relative to the noise in the global signal. Among the three mechanisms, the SUM rule produces the most accurate boundary. However, in contrast to the other two mechanisms, it requires noise to exit metastable states and rapidly reach the stable boundary pattern.

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