Many features of vertebrate bodies, such as the skeleton and the limbs, display symmetry between left and right. By contrast, the internal organs exhibit left-right asymmetries in their position and structure.
We use genetic, genomic, and imaging procedures to understand the basis of these symmetries and asymmetries during development and growth. We are also interested in how they contribute to human diseases including birth defects and scoliosis.
For our work, we primarily use the zebrafish model organism.
How is symmetry broken?
In many vertebrates, embryonic left-right symmetry is broken by an asymmetrical fluid flow generated by beating cilia (reviewed in Grimes and Burdine, Trends in Genetics, 2017). Sensation of that flow - which also depends on cilia - requires Polycystin family transmembrane proteins (Grimes et al., Plos Genetics, 2016). We study the pathways by which flow signals are transduced and ask how these pathways control the emergence of left-right asymmetries in the embryo.
How does the spine retain symmetry?
The spine is the defining feature of vertebrate life, but how it remains straight during growth is a mystery. In zebrafish mutants that lack cilia motility, cerebrospinal fluid flow is compromised. This results in late-onset spinal curves that appear during a growth spurt (Grimes et al., Science, 2016). These mutants closely model the human disease idiopathic scoliosis, the presence of abnormal 3D spinal curves that often occurs in adolescence. We apply micro-computed tomography, CRISPR mutagenesis, and single cell techniques to understand the roles of cilia and flows in maintaining spinal symmetry and to model idiopathic scoliosis.
