INVESTIGADORES
CHERNOMORETZ Ariel
artículos
Título:
Identification and functional analysis of healing regulators in Drosophila.
Autor/es:
C. ALVAREZ-FERNANDEZ; S. TAMIRISA; F. PRADA; A. CHERNOMORETZ; O. PODHAJCER; E. BLANCO; E. MARTIN-BLANCO
Revista:
PLOS GENETICS
Editorial:
PUBLIC LIBRARY SCIENCE
Referencias:
Lugar: San Francisco; Año: 2015 vol. 11
ISSN:
1553-7390
Resumen:
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.