Regulación epigenética de la condrogénesis y la muerte celular programada durante el desarrollo embrionario de las extremidades

Abstract

During embryonic development, the intense and continuous growth of the structures that will constitute the body shares space and time with processes of programmed cell death. A remarkable event of massive embryonic cell death occurs in the interdigital tissue during digit formation in the developing limb of vertebrates. Although for decades the cellular and molecular bases of these remodeling processes have been the focus of numerous investigations; nowadays, some of these mechanisms are still unknown. In our study, we described that prior to caspase activation, cells fated to die showed the activation of a DNA damage response (DDR). Considering the sequence of degeneration, DNA damage would be the primary event during interdigit regression, while senescence and apoptosis would occur downstream (Montero et al., 2016). Furthermore, we have found evidences of the implication of the epigenetic status of interdigital cells, via regulation of DNA methylation, in the remodeling process associated with the formation of free digits. This epigenetic modification seems to play a key role in the balance between differentiation and cell potential, a critical step in the initiation of programmed cell death associated with embryonic morphology (Sanchez-Fernandez et al., 2019).