Organogenesis and functional genomics of the endocrine pancreas

Nuria C. Bramswig, Klaus H. Kaestner

Functional genomics, the analysis of the wealth of data produced by genome-wide analyses of gene expression, protein-protein, and protein-DNA interactions, has revolutionized biomedical research. Our ability to determine global gene expression profiles, transcription factor-binding sites, and histone modification maps using microarray-based technologies and next-generation sequencing applications has greatly enhanced our understanding of gene regulatory networks and the molecular wiring diagrams of cells and tissues. The organogenesis of the endocrine pancreas involves numerous signaling events within the endoderm-derived pancreatic epithelium and the surrounding mesenchyme, as well as complex transcription factor networks. Detailed understanding of the differentiation process from foregut endoderm to mature endocrine cells has enabled the rational design of in vitro differentiation protocols that coax embryonic stem cells into β-like cells that might enable cell replacement therapy for diabetes in the future. In this review, we summarize the research studies that have utilized genomic tools to elucidate endocrine pancreatic organogenesis.