Ken Cho

Bone Morphogenetic Proteins (BMPs) signaling: – The BMP signaling pathway is a conserved and evolutionarily ancient regulatory module affecting a large variety of cellular behaviors. The evolutionary flexibility in utilizing BMP responses presumably arose by co-option of a canonical BMP signaling cascade to regulate the transcription of diverse batteries of target genes. This begs the question of how seemingly interchangeable BMP signaling components elicit widely different outputs in different cell types, an important issue in the context of understanding how BMP signaling integrates with gene regulatory networks to control development. We have identified a core BMP-responsive element (BRE) that responds specifically to BMP signaling in Drosophila, Xenopus, zebrafish and mouse. The BRE-mediated BMP responsiveness is mediated by a critical phylogenetically-conserved transcription factor (Schnurri-related zinc finger protein). We have developed a transgenic BRE-lacZ mouse line and a BRE-eGFP zebrafish line that respond to BMP signaling in a dynamic pattern consistent with many known sites of BMP signaling events during mouse and zebrafish embryogenesis. At the same time, we have initiated ChIP experiments to further uncover Schnurri’s regulatory mode.

Gene regulatory Network – Emergence of the primary germ layers is among the earliest events of cell specification in animal development. Understanding the mechanisms of germ layer formation and subsequent patterning has implications for the treatment of human disease. Our goal is to describe the underlying logic of genetic programs regulating vertebrate mesendoderm development. Traditionally, Gene Regulatory Network (GRN)s have been constructed using a combination of mapping of transcription factor (TF) binding sites, physical binding of TFs to these sites, and demonstration of the importance of both to gene expression output. This approach is both labor and time intensive. Another approach, utilizing a combination of computational methods with extensive perturbation analysis, can produce a GRN that, while lacking in the details of direct physical interactions, has the advantage of rapidly generating a global perspective. We generated large transcriptome profiles from tightly spaced stages of early Xenopus embryogenesis to permit modeling of the dynamics of changes in transcript levels. These data are incorporated along with morpholino knockdown studies to perturb relevant gene expression. Computational modeling has been used to identify critical core networks regulating endodermal development.

Recent Publications