The retinoic acid signaling pathway, a metabolite produced from vitamin A, is a key mechanism during embryonic development. It is involved in the formation of the anteroposterior pattern of the nervous system and the heart, and also intervenes in processes such as the formation of limbs.
A study by the Andalusian Center for Developmental Biology (CABD) led by José Maria Santos Pereiranow at the University of Seville and the Institute of Biomedicine Seville (IBiS), explains how this essential signaling pathway is capable of altering the expression of cellular genes, leading to the formation of different cell types and, as a result, from different body parts.
The research group used zebrafish embryos as a model organism and found that this signaling pathway initiates its specific gene expression program by activating a variety of regulatory elements. These are DNA sequences it works like this Switch turn the genes on or off.
Lourdes Gallardoone of the co-authors of the paper, points out that “when we treat embryos with retinoic acid, we observe greater activation of these embryos.” Switch thanks to the association of transcription factors, the molecules responsible for activation Switch“.
When we treated embryos with retinoic acid, we observed greater activation of these switches thanks to the binding of transcription factors
Transcription factors, which include the retinoic acid receptor itself and other factors activated by it, such as factors of the Hox, Meis and Sox families, modulate gene expression thanks to the creation of three-dimensional contacts between Switch and their target genes.
The finding is particularly important because the retinoic acid signaling pathway is essential for the correct embryonic development of vertebrates. Furthermore, this discovery provides a molecular mechanism that occurs in vivo, Signaling pathways contribute to the development of different cell types through changes in the three-dimensional structure of their genome and consequently cause changes in gene expression.
New avenues for future research
Marta Moreno, another co-author of the paper, comments: “This study opens up numerous possibilities for future research.” First, they have discovered a previously undescribed relationship between retinoic acid receptors and Sox3 transcription factor, which is involved in the formation of the nervous system, which could lead to new research results in this direction. Most importantly, it opens the possibility to further investigate how transcription factors can mediate changes in the three-dimensional folding of the genome to alter gene expression.
The use of single-cell technologies in a complex model such as zebrafish embryos can clarify how this mechanism occurs in different cell types and what consequences its change has on the cellular composition of the embryo.
This also has important implications for the human diseasesas there is increasing evidence that changes in the three-dimensional structure of the genome cause diseases such as hereditary malformations, cancer and neurodegenerative diseases.
Reference:
José M. Santos-Pereira et al. “Rewiring of the epigenome and chromatin architecture by exogenously induced retinoic acid signaling during zebrafish embryonic development”. Nucleic acid research