Research Interests

We are interested in how cells become sequentially determined to more precisely defined fates during vertebrate embryonic development, and how this process depends upon cell position and upon interactions among neighboring cells. To address these questions, we use genetics, molecular biology, time-lapse imaging, and embryology to investigate muscle patterning and segmentation in the zebrafish embryo.

Current Projects

Mesodermal segmentation. In all vertebrates, the trunk and tail mesoderm becomes segmented into a reiterated series of tissue blocks called somites that will later contribute to the axial skeleton and musculature. Somitogenesis is regulated both spatially and temporally and is controlled by the segmentation clock and by cell-cell interactions among presomitic cells. To understand how cyclic gene expression is regulated, we constructed a transgenic line that allows us to follow oscillating gene expression in single cells in live wildtype and mutant embryos. Using this line, we are investigating the function of candidate regulators in starting, stopping, and synchronizing the segmentation clock. To uncover the molecular nature of the segmentation clock, we have performed genetic screens to identify and characterize genes that disrupt cyclic gene expression when mutated. Some of the genes we've discovered are likely also involved in oscillatory gene expression in other cell types and tissues.

Cellular interactions during somitogenesis. In addition to studying the dynamic cell behaviors that occur prior to segmentation, we also use a variety of approaches to study somitic cell behaviors during and after segmentation. To understand mutant phenotypes, and thus gene function, at the level of single cells, we use time-lapse microscopy of wild-type and mutant embryos to observe cell-cell contacts and interactions occurring before, during, and after somites form.

Regulation of myogenic progenitor cells during regeneration and disease. Muscle stem cells, termed satellite cells, are critical for muscle regeneration after injury, and we and others are elucidating the molecular mechanisms regulating satellite cell maintenance, proliferation, and differentiation. We have found “satellite-like” myogenic progenitor cells in adult zebrafish skeletal muscle and are characterizing their proliferation and differentiation during muscle regeneration. Additionally, we are interested in identifying genes and pathways regulating satellite-like cells and muscle regeneration in healthy muscle tissue, after muscle injury, in zebrafish models of muscular dystrophy.

Publications

Complete list of publications (including BioRxiv submissions)