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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Autores principales: Álvarez-Fernández, C., Tamirisa, S., Prada, F., Chernomoretz, A., Podhajcer, O., Blanco, E., Martín-Blanco, E.
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_15537390_v11_n2_p1_AlvarezFernandez
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spelling 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
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AT pradaf identificationandfunctionalanalysisofhealingregulatorsindrosophila
AT chernomoretza identificationandfunctionalanalysisofhealingregulatorsindrosophila
AT podhajcero identificationandfunctionalanalysisofhealingregulatorsindrosophila
AT blancoe identificationandfunctionalanalysisofhealingregulatorsindrosophila
AT martinblancoe identificationandfunctionalanalysisofhealingregulatorsindrosophila
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