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Focal adhesion kinase-mediated signaling controls the onset of pancreatic cell differentiation
Signals from the endothelium play a pivotal role in pancreatic lineage commitment. As such, the fate of the epithelial cells relies heavily on the spatiotemporal recruitment of the endothelial cells to the embryonic pancreas. Although it is known that VEGFA secreted by the epithelium recruits the en...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482336/ https://www.ncbi.nlm.nih.gov/pubmed/36017799 http://dx.doi.org/10.1242/dev.200761 |
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author | Rodriguez, Uylissa A. Dahiya, Shakti Raymond, Michelle L. Gao, Chenxi Martins-Cargill, Christina P. Piganelli, Jon D. Gittes, George K. Hu, Jing Esni, Farzad |
author_facet | Rodriguez, Uylissa A. Dahiya, Shakti Raymond, Michelle L. Gao, Chenxi Martins-Cargill, Christina P. Piganelli, Jon D. Gittes, George K. Hu, Jing Esni, Farzad |
author_sort | Rodriguez, Uylissa A. |
collection | PubMed |
description | Signals from the endothelium play a pivotal role in pancreatic lineage commitment. As such, the fate of the epithelial cells relies heavily on the spatiotemporal recruitment of the endothelial cells to the embryonic pancreas. Although it is known that VEGFA secreted by the epithelium recruits the endothelial cells to the specific domains within the developing pancreas, the mechanism that controls the timing of such recruitment is poorly understood. Here, we have assessed the role of focal adhesion kinase (FAK) in mouse pancreatic development based on our observation that the presence of the enzymatically active form of FAK (pFAK) in the epithelial cells is inversely correlated with vessel recruitment. To study the role of FAK in the pancreas, we conditionally deleted the gene encoding focal adhesion kinase in the developing mouse pancreas. We found that homozygous deletion of Fak (Ptk2) during embryogenesis resulted in ectopic epithelial expression of VEGFA, abnormal endothelial recruitment and a delay in endocrine and acinar cell differentiation. The heterozygous mutants were born with no pancreatic phenotype but displayed gradual acinar atrophy due to cell polarity defects in exocrine cells. Together, our findings imply a role for FAK in controlling the timing of pancreatic lineage commitment and/or differentiation in the embryonic pancreas by preventing endothelial recruitment to the embryonic pancreatic epithelium. |
format | Online Article Text |
id | pubmed-9482336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-94823362022-10-25 Focal adhesion kinase-mediated signaling controls the onset of pancreatic cell differentiation Rodriguez, Uylissa A. Dahiya, Shakti Raymond, Michelle L. Gao, Chenxi Martins-Cargill, Christina P. Piganelli, Jon D. Gittes, George K. Hu, Jing Esni, Farzad Development Research Article Signals from the endothelium play a pivotal role in pancreatic lineage commitment. As such, the fate of the epithelial cells relies heavily on the spatiotemporal recruitment of the endothelial cells to the embryonic pancreas. Although it is known that VEGFA secreted by the epithelium recruits the endothelial cells to the specific domains within the developing pancreas, the mechanism that controls the timing of such recruitment is poorly understood. Here, we have assessed the role of focal adhesion kinase (FAK) in mouse pancreatic development based on our observation that the presence of the enzymatically active form of FAK (pFAK) in the epithelial cells is inversely correlated with vessel recruitment. To study the role of FAK in the pancreas, we conditionally deleted the gene encoding focal adhesion kinase in the developing mouse pancreas. We found that homozygous deletion of Fak (Ptk2) during embryogenesis resulted in ectopic epithelial expression of VEGFA, abnormal endothelial recruitment and a delay in endocrine and acinar cell differentiation. The heterozygous mutants were born with no pancreatic phenotype but displayed gradual acinar atrophy due to cell polarity defects in exocrine cells. Together, our findings imply a role for FAK in controlling the timing of pancreatic lineage commitment and/or differentiation in the embryonic pancreas by preventing endothelial recruitment to the embryonic pancreatic epithelium. The Company of Biologists Ltd 2022-09-09 /pmc/articles/PMC9482336/ /pubmed/36017799 http://dx.doi.org/10.1242/dev.200761 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Rodriguez, Uylissa A. Dahiya, Shakti Raymond, Michelle L. Gao, Chenxi Martins-Cargill, Christina P. Piganelli, Jon D. Gittes, George K. Hu, Jing Esni, Farzad Focal adhesion kinase-mediated signaling controls the onset of pancreatic cell differentiation |
title | Focal adhesion kinase-mediated signaling controls the onset of pancreatic cell differentiation |
title_full | Focal adhesion kinase-mediated signaling controls the onset of pancreatic cell differentiation |
title_fullStr | Focal adhesion kinase-mediated signaling controls the onset of pancreatic cell differentiation |
title_full_unstemmed | Focal adhesion kinase-mediated signaling controls the onset of pancreatic cell differentiation |
title_short | Focal adhesion kinase-mediated signaling controls the onset of pancreatic cell differentiation |
title_sort | focal adhesion kinase-mediated signaling controls the onset of pancreatic cell differentiation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482336/ https://www.ncbi.nlm.nih.gov/pubmed/36017799 http://dx.doi.org/10.1242/dev.200761 |
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