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David Jonah Grunwald

Professor of Human Genetics

B.A. Williams College

Ph.D. University of Wisconsin, Madison

Research

References

grunwald@genetics.utah.edu

 

Research

A major goal in the laboratory is to understand gene functions that regulate how precursor cells in specific regions of the embryo acquire specialized tissue functions. We work with zebrafish, because of the precision with which tissue development can be monitored in the nearly transparent, rapidly developing zebrafish embryo, and the ease with which mutations can be isolated and gene expression can be perturbed.   Because cellular and genetic processes of embryonic development are shared among all vertebrates, we can use the zebrafish to gain broad insights into developmental processes and to model specific inherited congenital defects that arise in humans.

A major focus of the lab is the role of T-box genes in coordinating the development of neighboring tissues. Mutations in T-box genes, which encode related transcription factors, are associated with congenital defects of the heart, limb, and other organ systems in humans.   A confounding feature of the defects caused by these mutations is that multiple tissue types appear affected making it difficult to discern a single primary cellular problem.   Our work helps understand why this occurs and how to analyze the primary defects that immediately result from loss of T-box gene function.   We have shown that multiple T-box genes are expressed as overlapping domains that form a quilt-like pattern in the embryo and that a critical determinant of a precursor cell's fate is the combination of T-box genes expressed by the cell.   Hence loss of function of a single T-box gene perturbs many different combinations of T-box genes and many types of precursor cells.   Our current work is aimed at using microarray analysis of T-box mutants in the zebrafish to identify the immediate target genes controlled by T-box transcription factors and to understand how combinations of co-expressed T-box factors interact to control downstream gene expression.  

A second focus of the lab aims to define the sequence of gene actions that leads to establishment of the neural crest, a multipotential precursor population that contributes to craniofacial, heart, pigmented, and neural tissues.   Using mutants we and others have isolated, we are identifying the signaling pathways that govern the initial induction and proliferation of the progenitor cells that give rise to the neural crest.  

A third focus in the lab utilizes the zebrafish to model congenital muscular dystrophies.   Our goal in these studies is to identify the primary cell differentiation defects that occur during embryogenesis and that lead to the congenital syndrome.

References