Identification and Functional Analysis of Healing Regulators in Drosophila
Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the overall steps in wound healing, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila...
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todo:paper_15537390_v11_n2_p1_AlvarezFernandez2023-10-03T16:25:31Z Identification and Functional Analysis of Healing Regulators in Drosophila Álvarez-Fernández, C. Tamirisa, S. Prada, F. Chernomoretz, A. Podhajcer, O. Blanco, E. Martín-Blanco, E. chaperonin containing TCP1 actin stress activated protein kinase actin filament adult animal cell animal tissue arc1 gene Article chemical analysis controlled study Drosophila female gene gene expression profiling gene function gene identification gene overexpression gene product genetic analysis in vitro study male nonhuman nucleotide sequence PDGF gene rho1 gene serpin55B gene tissue repair VEGF gene wound healing animal cytoskeleton Drosophila melanogaster epithelium gene expression regulation genetics growth, development and aging human imaginal disc insect genome metabolism pathology regeneration signal transduction thorax wound healing Mammalia Murinae Actins Animals Cytoskeleton Drosophila melanogaster Epithelium Gene Expression Regulation Genome, Insect Humans Imaginal Discs JNK Mitogen-Activated Protein Kinases MAP Kinase Signaling System Regeneration Signal Transduction Thorax Wound Healing Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the overall steps in wound healing, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process. However, they do allow the less understood aspects of the healing response to be explored, e.g., which signal(s) are responsible for initiating tissue remodeling? How is sealing of the epithelia achieved? Or, what inhibitory cues cancel the healing machinery upon completion? Answering these and other questions first requires the identification and functional analysis of wound specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method that is healing-permissive and that allows live imaging and biochemical analysis of cultured imaginal discs. We performed comparative genome-wide profiling between Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. Sets of potential wound-specific genes were subsequently identified. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in healing assays. This non-saturated analysis defines a relevant set of genes whose changes in expression level are functionally significant for proper tissue repair. Amongst these we identified the TCP1 chaperonin complex as a key regulator of the actin cytoskeleton essential for the wound healing response. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound healing response. © 2015 Álvarez-Fernández et al. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15537390_v11_n2_p1_AlvarezFernandez |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
chaperonin containing TCP1 actin stress activated protein kinase actin filament adult animal cell animal tissue arc1 gene Article chemical analysis controlled study Drosophila female gene gene expression profiling gene function gene identification gene overexpression gene product genetic analysis in vitro study male nonhuman nucleotide sequence PDGF gene rho1 gene serpin55B gene tissue repair VEGF gene wound healing animal cytoskeleton Drosophila melanogaster epithelium gene expression regulation genetics growth, development and aging human imaginal disc insect genome metabolism pathology regeneration signal transduction thorax wound healing Mammalia Murinae Actins Animals Cytoskeleton Drosophila melanogaster Epithelium Gene Expression Regulation Genome, Insect Humans Imaginal Discs JNK Mitogen-Activated Protein Kinases MAP Kinase Signaling System Regeneration Signal Transduction Thorax Wound Healing |
spellingShingle |
chaperonin containing TCP1 actin stress activated protein kinase actin filament adult animal cell animal tissue arc1 gene Article chemical analysis controlled study Drosophila female gene gene expression profiling gene function gene identification gene overexpression gene product genetic analysis in vitro study male nonhuman nucleotide sequence PDGF gene rho1 gene serpin55B gene tissue repair VEGF gene wound healing animal cytoskeleton Drosophila melanogaster epithelium gene expression regulation genetics growth, development and aging human imaginal disc insect genome metabolism pathology regeneration signal transduction thorax wound healing Mammalia Murinae Actins Animals Cytoskeleton Drosophila melanogaster Epithelium Gene Expression Regulation Genome, Insect Humans Imaginal Discs JNK Mitogen-Activated Protein Kinases MAP Kinase Signaling System Regeneration Signal Transduction Thorax Wound Healing Álvarez-Fernández, C. Tamirisa, S. Prada, F. Chernomoretz, A. Podhajcer, O. Blanco, E. Martín-Blanco, E. Identification and Functional Analysis of Healing Regulators in Drosophila |
topic_facet |
chaperonin containing TCP1 actin stress activated protein kinase actin filament adult animal cell animal tissue arc1 gene Article chemical analysis controlled study Drosophila female gene gene expression profiling gene function gene identification gene overexpression gene product genetic analysis in vitro study male nonhuman nucleotide sequence PDGF gene rho1 gene serpin55B gene tissue repair VEGF gene wound healing animal cytoskeleton Drosophila melanogaster epithelium gene expression regulation genetics growth, development and aging human imaginal disc insect genome metabolism pathology regeneration signal transduction thorax wound healing Mammalia Murinae Actins Animals Cytoskeleton Drosophila melanogaster Epithelium Gene Expression Regulation Genome, Insect Humans Imaginal Discs JNK Mitogen-Activated Protein Kinases MAP Kinase Signaling System Regeneration Signal Transduction Thorax Wound Healing |
description |
Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the overall steps in wound healing, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process. However, they do allow the less understood aspects of the healing response to be explored, e.g., which signal(s) are responsible for initiating tissue remodeling? How is sealing of the epithelia achieved? Or, what inhibitory cues cancel the healing machinery upon completion? Answering these and other questions first requires the identification and functional analysis of wound specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method that is healing-permissive and that allows live imaging and biochemical analysis of cultured imaginal discs. We performed comparative genome-wide profiling between Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. Sets of potential wound-specific genes were subsequently identified. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in healing assays. This non-saturated analysis defines a relevant set of genes whose changes in expression level are functionally significant for proper tissue repair. Amongst these we identified the TCP1 chaperonin complex as a key regulator of the actin cytoskeleton essential for the wound healing response. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound healing response. © 2015 Álvarez-Fernández et al. |
format |
JOUR |
author |
Álvarez-Fernández, C. Tamirisa, S. Prada, F. Chernomoretz, A. Podhajcer, O. Blanco, E. Martín-Blanco, E. |
author_facet |
Álvarez-Fernández, C. Tamirisa, S. Prada, F. Chernomoretz, A. Podhajcer, O. Blanco, E. Martín-Blanco, E. |
author_sort |
Álvarez-Fernández, C. |
title |
Identification and Functional Analysis of Healing Regulators in Drosophila |
title_short |
Identification and Functional Analysis of Healing Regulators in Drosophila |
title_full |
Identification and Functional Analysis of Healing Regulators in Drosophila |
title_fullStr |
Identification and Functional Analysis of Healing Regulators in Drosophila |
title_full_unstemmed |
Identification and Functional Analysis of Healing Regulators in Drosophila |
title_sort |
identification and functional analysis of healing regulators in drosophila |
url |
http://hdl.handle.net/20.500.12110/paper_15537390_v11_n2_p1_AlvarezFernandez |
work_keys_str_mv |
AT alvarezfernandezc identificationandfunctionalanalysisofhealingregulatorsindrosophila AT tamirisas identificationandfunctionalanalysisofhealingregulatorsindrosophila AT pradaf identificationandfunctionalanalysisofhealingregulatorsindrosophila AT chernomoretza identificationandfunctionalanalysisofhealingregulatorsindrosophila AT podhajcero identificationandfunctionalanalysisofhealingregulatorsindrosophila AT blancoe identificationandfunctionalanalysisofhealingregulatorsindrosophila AT martinblancoe identificationandfunctionalanalysisofhealingregulatorsindrosophila |
_version_ |
1807323194584989696 |