PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to Injury

To ensure proper wound healing it is important to elucidate the signaling cues that coordinate leader and follower cell behavior to promote collective migration and proliferation for wound healing in response to injury. Using an ex vivo post-cataract surgery wound healing model we investigated the r...

Full description

Bibliographic Details
Main Authors: Morgan D. Basta, A. Sue Menko, Janice L. Walker
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/21/3515
_version_ 1797468684819628032
author Morgan D. Basta
A. Sue Menko
Janice L. Walker
author_facet Morgan D. Basta
A. Sue Menko
Janice L. Walker
author_sort Morgan D. Basta
collection DOAJ
description To ensure proper wound healing it is important to elucidate the signaling cues that coordinate leader and follower cell behavior to promote collective migration and proliferation for wound healing in response to injury. Using an ex vivo post-cataract surgery wound healing model we investigated the role of class I phosphatidylinositol-3-kinase (PI3K) isoforms in this process. Our findings revealed a specific role for p110α signaling independent of Akt for promoting the collective migration and proliferation of the epithelium for wound closure. In addition, we found an important role for p110α signaling in orchestrating proper polarized cytoskeletal organization within both leader and wounded epithelial follower cells to coordinate their function for wound healing. p110α was necessary to signal the formation and persistence of vimentin rich-lamellipodia extensions by leader cells and the reorganization of actomyosin into stress fibers along the basal domains of the wounded lens epithelial follower cells for movement. Together, our study reveals a critical role for p110α in the collective migration of an epithelium in response to wounding.
first_indexed 2024-03-09T19:11:02Z
format Article
id doaj.art-05a73ca23274436f93da6ec1974d5978
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-09T19:11:02Z
publishDate 2022-11-01
publisher MDPI AG
record_format Article
series Cells
spelling doaj.art-05a73ca23274436f93da6ec1974d59782023-11-24T04:10:03ZengMDPI AGCells2073-44092022-11-011121351510.3390/cells11213515PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to InjuryMorgan D. Basta0A. Sue Menko1Janice L. Walker2Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USATo ensure proper wound healing it is important to elucidate the signaling cues that coordinate leader and follower cell behavior to promote collective migration and proliferation for wound healing in response to injury. Using an ex vivo post-cataract surgery wound healing model we investigated the role of class I phosphatidylinositol-3-kinase (PI3K) isoforms in this process. Our findings revealed a specific role for p110α signaling independent of Akt for promoting the collective migration and proliferation of the epithelium for wound closure. In addition, we found an important role for p110α signaling in orchestrating proper polarized cytoskeletal organization within both leader and wounded epithelial follower cells to coordinate their function for wound healing. p110α was necessary to signal the formation and persistence of vimentin rich-lamellipodia extensions by leader cells and the reorganization of actomyosin into stress fibers along the basal domains of the wounded lens epithelial follower cells for movement. Together, our study reveals a critical role for p110α in the collective migration of an epithelium in response to wounding.https://www.mdpi.com/2073-4409/11/21/3515collective migrationleader cellfollower cellwound healingPI3Kp110α
spellingShingle Morgan D. Basta
A. Sue Menko
Janice L. Walker
PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to Injury
Cells
collective migration
leader cell
follower cell
wound healing
PI3K
p110α
title PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to Injury
title_full PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to Injury
title_fullStr PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to Injury
title_full_unstemmed PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to Injury
title_short PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to Injury
title_sort pi3k isoform specific regulation of leader and follower cell function for collective migration and proliferation in response to injury
topic collective migration
leader cell
follower cell
wound healing
PI3K
p110α
url https://www.mdpi.com/2073-4409/11/21/3515
work_keys_str_mv AT morgandbasta pi3kisoformspecificregulationofleaderandfollowercellfunctionforcollectivemigrationandproliferationinresponsetoinjury
AT asuemenko pi3kisoformspecificregulationofleaderandfollowercellfunctionforcollectivemigrationandproliferationinresponsetoinjury
AT janicelwalker pi3kisoformspecificregulationofleaderandfollowercellfunctionforcollectivemigrationandproliferationinresponsetoinjury