Global analysis of the transcriptional network controllingXenopusendoderm formation

Abstract

A conserved molecular pathway has emerged controlling endoderm formation in Xenopus zebrafish and mice. Key genes in this pathway include Nodal ligands and transcription factors of the Mix-like paired homeodomain class, Gata4-6 zinc-finger factors and Sox17 HMG domain proteins. Although a linear epistatic pathway has been proposed, the precise hierarchical relationships between these factors and their downstream targets are largely unresolved. Here, we have used a combination of microarray analysis and loss-of-function experiments to examine the global regulatory network controlling Xenopus endoderm formation. We identified over 300 transcripts enriched in the gastrula endoderm, including most of the known endoderm regulators and over a hundred uncharacterized genes. Surprisingly only 10% of the endoderm transcriptome is regulated as predicted by the current linear model. We find that Nodal genes, Mixer and Sox17 have both shared and distinct sets of downstream targets, and that a number of unexpected autoregulatory loops exist between Sox17 and Gata4-6, between Sox17 and Bix1/Bix2/Bix4, and between Sox17 and Xnr4. Furthermore, we find that Mixer does not function primarily via Sox17 as previously proposed. These data provides new insight into the complexity of endoderm formation and will serve as valuable resource for establishing a complete endoderm gene regulatory network.

The role of FGF signaling in the establishment and maintenance of mesodermal gene expression in Xenopus

“…1H,O). There may also be a difference in regulation between endodermal transcripts, which reflects the intricate network of gene regulation involved in endoderm formation reported in array experiments (Dickinson et al, 2006;Sinner et al, 2006).…”

Klf5 regulates lineage formation in the pre-implantation mouse embryo

“…Cells in the pre-implantation embryo with reduced levels of Gata6 or Sox17 are impaired in PE contribution (Kanai-Azuma et al, 2002;Morris et al, 2010). In Xenopus, Sox17 has both Gatadependent and Gata-independent roles during endoderm formation (Sinner et al, 2006). Thus, Sox7 and Sox17 could function redundantly during PE differentiation and could act upstream of, or in parallel to, Gata factors.…”

TheGata5target,TGIF2, defines the pancreatic region by modulating BMP signals within the endoderm

“…Over the past few years extensive investigation has contributed to the elucidation of the molecular mechanisms underlying initial endoderm formation (Dickinson et al, 2006;Ober et al, 2003;Sinner et al, 2006;Tam et al, 2003;Taverner et al, 2005). However, we still know relatively little about subsequent endodermal patterning and how different domains of the endoderm progressively become specialized to generate distinct organ primordia.…”