BMP signaling coordinates gene expression and cell migration during precardiac mesoderm development

Gene regulatory networks control the progressive specification of cell types and govern morphogenetic events during development. However, how morphogenetic events reciprocally affect gene expression remains poorly understood. Here, we analyzed the function of BMP signaling and expression of downstream target genes during cell migration of the precardiac mesoderm (trunk ventral cells, TVCs) in ascidian embryos. Our results indicate that migrating TVCs experience increasing BMP signaling as they migrate towards the ventral trunk epidermis, which expresses sustained levels of Bmp2/4. This increasing signaling intensity allows the successive activation of GATAa, Tolloid, Bmp2/4 and NK4. Initial activation of GATAa, Tolloid and Bmp2/4 contribute to a positive feedback loop involving cell migration, chordin inhibition and BMP ligand production. Sustained levels of BMP signaling become sufficient to activate NK4 expression, which in turn contributes to a negative feedback loop inhibiting Bmp2/4 and Tolloid expression. In addition, NK4 appears to inhibit cell migration thus providing a "transcriptional brake" to stop TVC migration. Our observations led us to propose a model for the coordination of cell migration and gene expression based on the temporal unfolding of a gene regulatory sub-network in a relevant developmental context.