Autocrine inhibition of cell motility can drive epithelial branching morphogenesis in the absence of growth
| Autor: | Iraes Rabbers, Roeland M. H. Merks, Elisabeth G. Rens, Mathé T. Zeegers, András Szabó |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cellular differentiation
medicine.medical_treatment Mammary gland Epithelial Branching Models Biological General Biochemistry Genetics and Molecular Biology Cell Movement Branching Morphogenesis medicine Morphogenesis Animals Cellular Potts Model Autocrine signalling Cell Proliferation Stochastic Processes Cell growth Chemistry Growth factor Mesenchymal stem cell Cellular Potts model Cell migration Articles Collective cell behaviour Epithelium Cell biology Cell-based models Autocrine Communication medicine.anatomical_structure General Agricultural and Biological Sciences Developmental Biology |
| Zdroj: | Philosophical Transactions of the Royal Society of London Series B: Biological Sciences, 375(1807). The Royal Society Philosophical Transactions of the Royal Society B, 375(1807) Philos Trans R Soc Lond B Biol Sci |
| Popis: | Epithelial branching morphogenesis drives the development of organs such as the lung, salivary gland, kidney and the mammary gland. It involves cell proliferation, cell differentiation and cell migration. An elaborate network of chemical and mechanical signals between the epithelium and the surrounding mesenchymal tissues regulates the formation and growth of branching organs. Surprisingly, when cultured in isolation from mesenchymal tissues, many epithelial tissues retain the ability to exhibit branching morphogenesis even in the absence of proliferation. In this work, we propose a simple, experimentally plausible mechanism that can drive branching morphogenesis in the absence of proliferation and cross-talk with the surrounding mesenchymal tissue. The assumptions of our mathematical model derive fromin vitroobservations of the behaviour of mammary epithelial cells. These data show that autocrine secretion of the growth factor TGFβ1 inhibits the formation of cell protrusions, leading to curvature-dependent inhibition of sprouting. Our hybrid cellular Potts and partial-differential equation model correctly reproduces the experimentally observed tissue-geometry-dependent determination of the sites of branching, and it suffices for the formation of self-avoiding branching structures in the absence and also in the presence of cell proliferation.This article is part of the theme issue ‘Multi-scale analysis and modelling of collective migration in biological systems’. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|