RESUMEN
Tissue regeneration requires precise temporal control of cellular processes such as inflammatory signaling, chromatin remodeling and proliferation. The combination of these processes forms a unique microenvironment permissive to the expression, and potential mobilization of, transposable elements (TEs). Here, we develop the hypothesis that TE activation creates a barrier to tissue repair that must be overcome to achieve successful regeneration. We discuss how uncontrolled TE activity may impede tissue restoration and review mechanisms by which TE activity may be controlled during regeneration. We posit that the diversification and co-evolution of TEs and host control mechanisms may contribute to the wide variation in regenerative competency across tissues and species.
Asunto(s)
Elementos Transponibles de ADN , Evolución Molecular , Elementos Transponibles de ADN/genéticaRESUMEN
The ciliary marginal zone (CMZ) of the zebrafish retina contains a population of actively proliferating resident stem cells, which generate retinal neurons throughout life. The maintenance methyltransferase, dnmt1, is expressed within the CMZ. Loss of dnmt1 function results in gene misregulation and cell death in a variety of developmental contexts, however, its role in retinal stem cell (RSC) maintenance is currently unknown. Here, we demonstrate that zebrafish dnmt1s872 mutants possess severe defects in RSC maintenance within the CMZ. Using a combination of immunohistochemistry, in situ hybridization, and a transgenic reporter assay, our results demonstrate a requirement for dnmt1 activity in the regulation of RSC proliferation, gene expression and in the repression of endogenous retroelements (REs). Ultimately, cell death is elevated in the dnmt1-/- CMZ, but in a p53-independent manner. Using a transgenic reporter for RE transposition activity, we demonstrate increased transposition in the dnmt1-/- CMZ. Taken together our data identify a critical role for dnmt1 function in RSC maintenance in the vertebrate eye.