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Citation
Schilling, S., Willecke, M., Aegerter-Wilmsen, T., Cirpka, O.A., Basler, K., von Mering, C. (2011). Cell-sorting at the a/p boundary in the Drosophila wing primordium: a computational model to consolidate observed non-local effects of hh signaling.  PLoS Comput. Biol. 7(4): e1002025.
FlyBase ID
FBrf0213439
Publication Type
Research paper
Abstract

Non-intermingling, adjacent populations of cells define compartment boundaries; such boundaries are often essential for the positioning and the maintenance of tissue-organizers during growth. In the developing wing primordium of Drosophila melanogaster, signaling by the secreted protein Hedgehog (Hh) is required for compartment boundary maintenance. However, the precise mechanism of Hh input remains poorly understood. Here, we combine experimental observations of perturbed Hh signaling with computer simulations of cellular behavior, and connect physical properties of cells to their Hh signaling status. We find that experimental disruption of Hh signaling has observable effects on cell sorting surprisingly far from the compartment boundary, which is in contrast to a previous model that confines Hh influence to the compartment boundary itself. We have recapitulated our experimental observations by simulations of Hh diffusion and transduction coupled to mechanical tension along cell-to-cell contact surfaces. Intriguingly, the best results were obtained under the assumption that Hh signaling cannot alter the overall tension force of the cell, but will merely re-distribute it locally inside the cell, relative to the signaling status of neighboring cells. Our results suggest a scenario in which homotypic interactions of a putative Hh target molecule at the cell surface are converted into a mechanical force. Such a scenario could explain why the mechanical output of Hh signaling appears to be confined to the compartment boundary, despite the longer range of the Hh molecule itself. Our study is the first to couple a cellular vertex model describing mechanical properties of cells in a growing tissue, to an explicit model of an entire signaling pathway, including a freely diffusible component. We discuss potential applications and challenges of such an approach.

PubMed ID
PubMed Central ID
PMC3072364 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS Comput. Biol.
    Title
    PLoS Computational Biology
    Publication Year
    2005-
    ISBN/ISSN
    1553-7358 1553-734X
    Data From Reference
    Alleles (3)
    Genes (6)
    Insertions (1)
    Transgenic Constructs (1)