Systems Biology of Stem Cells and Embryonic Development

Systems-level analysis of vertebratal segmentation, stem cell proliferation and muscle differentiation
    Vertebrate body axis is composed of repetitive structures, called vertebrae. These metameric structures are established during embryonic development by a process called somitogenesis, where the precursors of vertebrae and associated muscles are laid down as sequential tissue segments (somites). The rhythmic production of the somites is controlled by the “segmentation clock” that reveals itself as oscillatory gene expression at the posterior (tail) end of the vertebrate embryos. Fgf, Wnt, Notch and Retinoic Acid (RA) signaling pathways interact with each other to regulate the somite segmentation and differentiation. Defects in somite segmentation and differentiation result in vertebral anomalies, congenital scoliosis, and mispatterning of intersomitic blood vessels and peripheral nerves. It is important to identify genes involved at different stages of segmentation in order to develop future gene- and cell-therapies for the patients. Cells segmented into somites differentiate into vertebrae and muscles. Muscle wasting (muscular atrophy) and muscular dystrophy develop due to genetic mutations, metabolic disorders and aging. It is crucial to discover the gene regulatory network that controls the differentiation of muscle cells to be able to induce adult muscle stem cells (satellite cells) to proliferate and differentiate. Also, the regulation of metabolism in muscle cells needs deeper understanding to prevent and cure metabolic defects, such as insulin resistance in muscle cells.
    In our lab, we focus on three major research areas:
1- Regulation of differentiation, growth and metabolism of muscles during embryogenesis
2- Control of vertebrate anterior-posterior axis extension: proliferation of stem cells at the posterior end of the embryo
3- Quantitative developmental biology: somite segmentation, gene expression oscillations, morphogen gradients.

    We aim to understand how these processes are controlled by the signaling pathways and their transcription factor targets. Genome-wide studies, molecular temporal-perturbation experiments and imaging will be coupled with bioinformatics tools and mathematical modeling to achieve these objectives and zebrafish will be utilized as the main model organism during these studies.