Abstract
Morphogen gradients are crucial for the development of organisms. The biochemical properties of many morphogens prevent their extracellular free diffusion, indicating the need of an active mechanism for transport. The involvement of filopodial structures (cytonemes) has been proposed for morphogen signaling. Here, we describe an in silico model based on the main general features of cytoneme-meditated gradient formation and its implementation into Cytomorph, an open software tool. We have tested the spatial and temporal adaptability of our model quantifying Hedgehog (Hh) gradient formation in two Drosophila tissues. Cytomorph is able to reproduce the gradient and explain the different scaling between the two epithelia. After experimental validation, we studied the predicted impact of a range of features such as length, size, density, dynamics and contact behavior of cytonemes on Hh morphogen distribution. Our results illustrate Cytomorph as an adaptive tool to test different morphogen gradients and to generate hypotheses that are difficult to study experimentally.
Highlights
IntroductionGroups of cells are organized to give rise to tissues and organs
During embryonic development, groups of cells are organized to give rise to tissues and organs
We have developed an in silico model for gradient formation based on key features of cytoneme mediated signaling
Summary
Groups of cells are organized to give rise to tissues and organs. Precise spatio-temporal control of cell-to-cell communication is needed during proliferation, cellular three-dimensional organization and differentiation. Misregulation of these events is one of the most prevalent causes of diseases such as congenital malformations, neurological disorders and cancer [1]. Models to explain pattern generation during development have been mainly focused on the description of how, when and where a morphogenetic signal induces a specific cellular response within a particular tissue. Increasing experimental evidences by live imaging in developing tissues highlight the implication of dynamic cytonemes in short- and long-distance cell communication [22,23,28,29,30]
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