Cascadas génicas en la morfogénesis de los vertebradosActivación independiente y similitud funcional de snail1 y prx1 en asimetría izquierda derecha y transición epitelio mesénquima

Resumen

In this work we show the relationship between different members of the BMP and Snail families. At morphogenetic stages, the expression of BMP2 is associated with that of Snail1 while the territories of BMP4 expression correlate with those expressing Snail2. These correlations hold true regardless of the tissues and species analyzed. As such, these genetic pathways seem to be conserved in avian and mammalian embryos during neural crest induction, left-right asymmetry and lateral plate mesoderm differentiation. A careful analysis in different tissues throughout morphogenesis support the idea that the interchange in expression sites between Snail1 and Snail2 in different vertebrates may be explained at least in part, by the interchange in the expression patterns of their corresponding inducers. We have found that in addition to Snail1, BMP2 can also induce the expression of the paired-related homeobox gene Prx1. As Snail1, Prx1 is asymmetrically expressed, exhibiting higher levels on the right than on the left lateral plate mesoderm in a highly dynamic and transient manner. This asymmetric expression is evolutionarily conserved and functional analysis in the zebrafish embryo show that, as Snail1, Prx1 also belongs to the molecular pathway controlling organ laterality. Furthermore, we show that Prx1 is activated by BMP2 and repressed by Nodal. Interestingly, the induction of Snail1 and Prx1 occurs in an independent manner, pointing to the existence of two parallel BMP2-dependent pathways. We have also found that Prx1 is a novel inducer of the epithelial-to-mesenchymal transition (EMT). Indeed, Prx1 induces the loss of epithelial markers including E-Cadherin and laminin, the gain of mesenchymal markers such as vimentin and the secretion of the extracellular matrix protein fibronectin. Concomitantly, Prx1 induces the acquisition of migratory and invasive properties. EMTs occur not only during embryonic development but also during tumoour progression. As Snail1, Prx1 al