Abstract: DNA damage independent of caspase activation accompanies programmed cell death in different
vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of
the interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves
oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM
precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association
of ?H2AX with other downstream DNA repair factors, including MDC1, Rad50 and 53BP1 suggests
a defensive response of cells against DNA damage. The relative distribution of cells ?H2AX-only
positive, TUNEL-only positive, and cells double positive for both markers is consistent with a sequence
of degenerative events starting by damage of the DNA. In support of this interpretation, the relative
number of ?H2AX-only cells increases after caspase inhibition while the relative number of TUNELonly
cells increases after inhibition of ATM. Furthermore, cultured interdigits survived and maintained
intense chondrogenic potential, even at advanced stages of degeneration, discarding a previous
commitment to die. Our findings support a new biological paradigm considering embryonic cell death
secondary to genotoxic stimuli, challenging the idea that considers physiological cell death a cell suicide
regulated by an internal death clock that pre-programmes degeneration.
Authorship: Montero J., Sanchez-Fernandez C., Lorda-Diez C., Garcia-Porrero J., Hurle J.,
Fuente: Scientific Reports, 2016, 6, 35478
Publisher: Nature Publishing Group
Year of publication: 2016
No. of pages: 12
Publication type: Article
DOI: 10.1038/srep35478
ISSN: 2045-2322
Publication Url: https://doi.org/10.1038/srep35478