Our goal is to build transcriptional GRNs regulating vertebrate endoderm/mesoderm formation so that someday we learn to respecify developmental fates using reverse engineering approaches.
Fertilized eggs give rise to many millions of cells, representing hundreds of different cell types, which eventually form the complex structures of the adult. Each dividing cell makes numerous specific decisions as to which genes to express among the tens of thousands of genes in its genome. If this tightly regulated process goes awry, an embryo may develop abnormalities or subsequently develop diseases as an adult. The regulatory programs that turn specific genes on or off are embedded in the genome of the organism. Therefore, a current major effort in biology is to understand the mechanisms by which gene networks are coordinated, thereby specifying paths of cellular differentiation. We use DNA microarrays to generate gene expression inventories and ChIP-on-Chip approach to examine transcriptional activities of transcription factors to obtain a holistic view of gene regulation. We focus on the very early stage of Xenopus embryogenesis, specifically at the stage when the germ layer specification and patterning of mesoderm and endoderm occurs. Our goal is to create GRNs involved in endomesoderm formation in vertebrates. This project is also tightly linked to our stem cell project, in which we attempt to regulate the differentiation of ES cells into different cell types. [see Koide et al., PNAS 2005]
Xenopus Endomesoderm GRN
BMP signaling and GRNs
Bone Morphogenetic Proteins (BMPs) are key players in a multitude of cell signaling events, from the subdivision of tissue types during early embryogenesis to the formation of limbs and internal organs. BMPs are involved in bone formation, neurogenesis and stem cell maintenance. Recently, we have identified a conserved BMP responsive element (BRE) within the promoter of Xvent2 and Id3 in Xenopus and found that the BRE is conserved in Drosophila, zebrafish, mice and humans. A key molecule mediating the signaling is the evolutionally conserved, large (~300kD) multi-zinc finger transcription factor Schnurri (Shn). Importantly, Shn has the ability to function as a transcriptional activator or repressor depending on the biological context. Since Shn appears to function as an evolutionarily conserved transcriptional factor involved in BMP signaling, our goal is to determine 1) the general design principles of BMP GRNs in verterbrates, 2) how conserved BMP signaling modules are deployed in different biological processes to provide specific cellular responses, and 3) the structural organization of cis-regulatory element regulating the process using both in vivo and in silico approaches. [see von Bubnoff et al. 2005; Yao et al., 2006]
Schunurri-Smad interaction
