Cell autonomous role of nuclear FGF in gene expression patterning during organogenesis

ABSTRACT: Cell signaling molecules are essential drivers of gene expression patterns, which are crucial for the development of multicellular organisms. Although prior research has established the importance of the levels and distribution of these molecules for gene expression patterns during embryonic development, a complete understanding of the specific targets influenced by their activity remains elusive. This study investigates how the fibroblast growth factor (FGF), a key developmental signal, orchestrates gene expression during the organogenesis of the zebrafish lateral line. Our analysis provides a detailed catalog of genes mediated by FGF signaling and identified dose-dependent genes that consistently respond to varying levels of extracellular FGF signaling in vivo. Notably, we uncovered an unexpected group of target genes that show suppressed expression at increased levels of FGF ligand, independent of changes in extracellular signaling. Experiments utilizing mosaic mis-expression of FGF ligands demonstrate that this gene regulation occurs autonomously within individual cells. In embryos with endogenous FGF levels, these target genes are suppressed in FGF-producing cells that shows nuclear accumulation of the FGF ligand. Targeted degradation of nuclear FGF confirms its role in this suppression, while not interfering with the activity of extracellular FGF signaling in the neighboring cells. Thus, we propose a novel mechanism of gene expression patterning in which the FGF ligand is directed to the nucleus within source cells. This process autonomously regulates its signaling targets, which are induced by extracellular FGF, leading to a self-organized symmetry-breaking in FGF signaling targets. Our findings of consistent gene expression patterns across multiple tissues, together with the nuclear localization of other paracrine FGF ligands, indicate that the cell-autonomous gene regulation by nuclear-targeted ligands could be a more widespread mechanism.

ORGANISM(S): Danio rerio

PROVIDER: GSE207538 | GEO | 2024/09/30

REPOSITORIES: GEO