INVESTIGADORES
STROBL MAZZULLA Pablo Hernan
artículos
Título:
Folate carrier deficiency drives differential methylation and enhanced cellular potency in the neural plate border
Autor/es:
ALATA JIMENEZ, NAGIF; STROBL-MAZZULLA, PABLO HERNÁN
Revista:
Frontiers in Cell and Developmental Biology
Editorial:
Frontiers Media S.A.
Referencias:
Año: 2022
ISSN:
2296-634X
Resumen:
The neural plate border (NPB) of vertebrate embryos segregates from the neural andepidermal regions, and it is comprised of an intermingled group of multipotent progenitorcells. Folate is the precursor of S-adenosylmethionine, the main methyl donor for DNAmethylation, and it is critical for embryonic development, including the specification ofprogenitors which reside in the NPB. Despite the fact that several intersecting signalsinvolved in the specification and territorial restriction of NPB cells are known, the role ofepigenetics, particularly DNA methylation, has been a matter of debate. Here, weexamined the temporal and spatial distribution of the methyl source and analyzed theabundance of 5mC/5 hmC and their epigenetic writers throughout the segregation of theneural and NPB territories. Reduced representation bisulfite sequencing (RRBS) onReduced Folate Carrier 1 (RFC1)-deficient embryos leads to the identification ofdifferentially methylated regions (DMRs). In the RFC1-deficient embryos, we identifiedseveral DMRs in the Notch1 locus, and the spatiotemporal expression of Notch1 and itsdownstream target gene Bmp4 were expanded in the NPB. Cell fate analysis on folatedeficient embryos revealed a significant increase in the number of cells coexpressing bothneural (SOX2) and NPB (PAX7) markers, which may represent an enhancing effect in thecellular potential of those progenitors. Taken together, our findings propose a model wherethe RFC1 deficiency drives methylation changes in specific genomic regions that arecorrelated with a dysregulation of pathways involved in early development such asNotch1 and BMP4 signaling. These changes affect the potency of the progenitorsresiding in the juncture of the neural plate and NPB territories, thus driving them to aprimed state.
