Genetic analysis of the genes important for adult form and function

Developmental genetics

The focus of the lab is to use forward genetics to systematically identify genes that are essential for the generation of adult form and physiology. The zebrafish has been the primary model organism due to the ease of large scale genetic screens in this fish. We reason that due to the selection within the screen design that the types of genes mutated would be biased to those that were more likely to be seen in nature and in human disease. Initial work shows that this is indeed the case and we have identified mutant models for human skeletal diseases that have facilitated use of the zebrafish to study the etiology of skeletal disease. Recent work is centered on identification of adult specific stem cell populations in regulating postembryonic development and the onset of aging pathologies.

Mapping of mutants through whole genome sequencing

In tandem, similar to mapping of genes from mutagenesis in the lab, we use comparative genetic tools to map the genetic changes associated with trait change in evolution. Thus, we leverage Nature’s experiments to identify genetic changes associated with the formation of novel forms and physiologies. We then mirror these genetic shifts in the zebrafish and ask if these genetic variations are sufficient to cause the observed change in phenotypic. We have called this methodology, Phylomapping. Use of this method, as well as recent TRACCER comparative tools, has led to a detailed understanding of the causes of trait variation to accommodate extreme environments, extreme longevity, and fin proportion. Together, our genetic analysis has produced a large number of different phenotypes that reveal new genetic and developmental mechanisms essential for late developmental processes. This work has enormous potential to uncover developmental processes important in the generation of complex form in vertebrates that have both medical and evolutionary importance.