New paradigm in cellular communication

A publication just came out in Nature Communications about an important revealing study that tries to contribute to understand the process of how cells communicate. The publication

A. Aguirre-Tamaral, M. Cambón, D. Poyato, J. Soler I. Guerrero, Predictive model for cytoneme guidance in Hedghog signaling based on Ihog-Glypicans interactions. Nature Communications. 13 (2022), 5647.

is freely accessible and can be downloaded together with the supplementary material at

The paper is the result of interdisciplinary work coordinated by professors Isabel Guerrero (Center for Molecular Biology, CBM, Severo Ochoa, CSIC, Madrid) and Juan Soler (Department of Applied Mathematics, University of Granada, UGR). The list of authors is completed by Adrián Aguirre-Tamaral (CBM, CSIC), Manuel Cambón and David Poyato (UGR). All researchers are members of the MNat unit of excellence.

During embryonic development, cell-cell communication is crucial in coordinating cell behavior, especially in the generation of differentiation patterns across morphogen gradients. Morphogens are signaling molecules secreted by source cells that elicit concentration-dependent responses in target cells. For several morphogens, cell-cell contact via filopodia-like structures (cytonemes) has been proposed as a mechanism for gradient formation. Despite advances in cytoneme signaling, little was known about how cytonemes navigate through the extracellular matrix and how they orient themselves to find their target.

In this work it is shown that the differences in the stabilization and orientation of the cytoneme depend on the relative levels of certain proteins, whose concentration generates flows of polarized orientation (repulsive or attractive) as electric fields. In feedback between mathematical modeling (generic enough to be applied to the study of other morphogens) and biological experimentation, the Hedgehog (Hh) morphogen signaling pathway has been studied, which is involved in both cell growth and renewal, when it is regulated, as in tumor spread, when it is unregulated.

In the case of Hh, the adhesion protein Interference hedgehog (Ihog) and the glypicans Dally and Dally-like-protein (Dlp) interact, act as concentrations to define a field that is responsible for the orientation, stabilization and behavior of the cytoneme in its mission to communicate with the other cells.

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