INVESTIGADORES
MUNARRIZ Eliana Rosa
artículos
Título:
Apaf1-dependent programmed cell death is required for inner ear morphogenesis and growth.
Autor/es:
CECCONI F, ROTH KA, DOLGOV O, MUNARRIZ E, ANOKHIN K, GRUSS P, SALMINEN M.
Revista:
DEVELOPMENT
Editorial:
COMPANY OF BIOLOGISTS LTD
Referencias:
Año: 2004 p. 2125 - 2135
ISSN:
0950-1991
Resumen:
During inner ear development programmed cell death occurs in specific
areas of the otic epithelium but the significance of it and the
molecules involved have remained unclear. We undertook an analysis of
mouse mutants in which genes encoding apoptosis-associated molecules
have been inactivated. Disruption of the Apaf1 gene led to a dramatic
decrease in apoptosis in the inner ear epithelium, severe morphogenetic
defects and a significant size reduction of the membranous labyrinth,
demonstrating that an Apaf1-dependent apoptotic pathway is necessary for
normal inner ear development. This pathway most probably operates
through the apoptosome complex because caspase 9 mutant mice suffered
similar defects. Inactivation of the Bcl2-like (Bcl2l) gene led to an
overall increase in the number of cells undergoing apoptosis but did not
cause any major morphogenetic defects. In contrast, decreased apoptosis
was observed in specific locations that suffered from developmental
deficits, indicating that proapoptotic isoform(s) produced from Bcl2l
might have roles in inner ear development. In Apaf1(-/-)/Bcl2l(-/-)
double mutant embryos, no cell death could be detected in the otic
epithelium, demonstrating that the cell death regulated by the
anti-apoptotic Bcl2l isoform, Bcl-X(L) in the otic epithelium is
Apaf1-dependent. Furthermore, the otic vesicle failed to close
completely in all double mutant embryos analyzed. These results indicate
important roles for both Apaf1 and Bcl2l in inner ear development.