Cell-sorting at the A/P boundary in the Drosophila wing primordium: a computational model to consolidate observed non-local effects of Hh signaling.

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...

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Autores principales:	Sabine Schilling, Maria Willecke, Tinri Aegerter-Wilmsen, Olaf A Cirpka, Konrad Basler, Christian von Mering
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/837df22938cf42c3834c3be2fa4cafe2
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spelling	oai:doaj.org-article:837df22938cf42c3834c3be2fa4cafe22021-11-18T05:50:36ZCell-sorting at the A/P boundary in the Drosophila wing primordium: a computational model to consolidate observed non-local effects of Hh signaling.1553-734X1553-735810.1371/journal.pcbi.1002025https://doaj.org/article/837df22938cf42c3834c3be2fa4cafe22011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21490725/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Non-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.Sabine SchillingMaria WilleckeTinri Aegerter-WilmsenOlaf A CirpkaKonrad BaslerChristian von MeringPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 4, p e1002025 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Sabine Schilling Maria Willecke Tinri Aegerter-Wilmsen Olaf A Cirpka Konrad Basler Christian von Mering Cell-sorting at the A/P boundary in the Drosophila wing primordium: a computational model to consolidate observed non-local effects of Hh signaling.
description	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.
format	article
author	Sabine Schilling Maria Willecke Tinri Aegerter-Wilmsen Olaf A Cirpka Konrad Basler Christian von Mering
author_facet	Sabine Schilling Maria Willecke Tinri Aegerter-Wilmsen Olaf A Cirpka Konrad Basler Christian von Mering
author_sort	Sabine Schilling
title	Cell-sorting at the A/P boundary in the Drosophila wing primordium: a computational model to consolidate observed non-local effects of Hh signaling.
title_short	Cell-sorting at the A/P boundary in the Drosophila wing primordium: a computational model to consolidate observed non-local effects of Hh signaling.
title_full	Cell-sorting at the A/P boundary in the Drosophila wing primordium: a computational model to consolidate observed non-local effects of Hh signaling.
title_fullStr	Cell-sorting at the A/P boundary in the Drosophila wing primordium: a computational model to consolidate observed non-local effects of Hh signaling.
title_full_unstemmed	Cell-sorting at the A/P boundary in the Drosophila wing primordium: a computational model to consolidate observed non-local effects of Hh signaling.
title_sort	cell-sorting at the a/p boundary in the drosophila wing primordium: a computational model to consolidate observed non-local effects of hh signaling.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/837df22938cf42c3834c3be2fa4cafe2
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Cell-sorting at the A/P boundary in the Drosophila wing primordium: a computational model to consolidate observed non-local effects of Hh signaling.

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