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In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis

The three-dimensional architecture of the pancreatic islet is integral to beta cell function, but the process of islet formation remains poorly understood due to the difficulties of imaging internal organs with cellular resolution. Within transparent zebrafish larvae, the developing pancreas is rela...

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Autores principales: Freudenblum, Julia, Iglesias, José A., Hermann, Martin, Walsen, Tanja, Wilfinger, Armin, Meyer, Dirk, Kimmel, Robin A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818004/
https://www.ncbi.nlm.nih.gov/pubmed/29386244
http://dx.doi.org/10.1242/dev.158477
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author Freudenblum, Julia
Iglesias, José A.
Hermann, Martin
Walsen, Tanja
Wilfinger, Armin
Meyer, Dirk
Kimmel, Robin A.
author_facet Freudenblum, Julia
Iglesias, José A.
Hermann, Martin
Walsen, Tanja
Wilfinger, Armin
Meyer, Dirk
Kimmel, Robin A.
author_sort Freudenblum, Julia
collection PubMed
description The three-dimensional architecture of the pancreatic islet is integral to beta cell function, but the process of islet formation remains poorly understood due to the difficulties of imaging internal organs with cellular resolution. Within transparent zebrafish larvae, the developing pancreas is relatively superficial and thus amenable to live imaging approaches. We performed in vivo time-lapse and longitudinal imaging studies to follow islet development, visualizing both naturally occurring islet cells and cells arising with an accelerated timecourse following an induction approach. These studies revealed previously unappreciated fine dynamic protrusions projecting between neighboring and distant endocrine cells. Using pharmacological compound and toxin interference approaches, and single-cell analysis of morphology and cell dynamics, we determined that endocrine cell motility is regulated by phosphoinositide 3-kinase (PI3K) and G-protein-coupled receptor (GPCR) signaling. Linking cell dynamics to islet formation, perturbation of protrusion formation disrupted endocrine cell coalescence, and correlated with decreased islet cell differentiation. These studies identified novel cell behaviors contributing to islet morphogenesis, and suggest a model in which dynamic exploratory filopodia establish cell-cell contacts that subsequently promote cell clustering.
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spelling pubmed-58180042018-02-28 In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis Freudenblum, Julia Iglesias, José A. Hermann, Martin Walsen, Tanja Wilfinger, Armin Meyer, Dirk Kimmel, Robin A. Development Research Article The three-dimensional architecture of the pancreatic islet is integral to beta cell function, but the process of islet formation remains poorly understood due to the difficulties of imaging internal organs with cellular resolution. Within transparent zebrafish larvae, the developing pancreas is relatively superficial and thus amenable to live imaging approaches. We performed in vivo time-lapse and longitudinal imaging studies to follow islet development, visualizing both naturally occurring islet cells and cells arising with an accelerated timecourse following an induction approach. These studies revealed previously unappreciated fine dynamic protrusions projecting between neighboring and distant endocrine cells. Using pharmacological compound and toxin interference approaches, and single-cell analysis of morphology and cell dynamics, we determined that endocrine cell motility is regulated by phosphoinositide 3-kinase (PI3K) and G-protein-coupled receptor (GPCR) signaling. Linking cell dynamics to islet formation, perturbation of protrusion formation disrupted endocrine cell coalescence, and correlated with decreased islet cell differentiation. These studies identified novel cell behaviors contributing to islet morphogenesis, and suggest a model in which dynamic exploratory filopodia establish cell-cell contacts that subsequently promote cell clustering. The Company of Biologists Ltd 2018-02-01 /pmc/articles/PMC5818004/ /pubmed/29386244 http://dx.doi.org/10.1242/dev.158477 Text en © 2018. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Freudenblum, Julia
Iglesias, José A.
Hermann, Martin
Walsen, Tanja
Wilfinger, Armin
Meyer, Dirk
Kimmel, Robin A.
In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis
title In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis
title_full In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis
title_fullStr In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis
title_full_unstemmed In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis
title_short In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis
title_sort in vivo imaging of emerging endocrine cells reveals a requirement for pi3k-regulated motility in pancreatic islet morphogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818004/
https://www.ncbi.nlm.nih.gov/pubmed/29386244
http://dx.doi.org/10.1242/dev.158477
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