Laura Rolfs will present a talk about his/her/their work entitled, “The role of non-muscle myosins in zebrafish development and MYH9-related disease”

The Abstract is as Follows:

MYH genes encode highly conserved actin-based motor proteins, non-muscle myosins (NMIIs), which have essential roles in cell division, cell migration, and cell shape changes. Zebrafish have two myh9 genes (myh9a and myh9b) which encode for the NMIIA protein, along with myh10 and myh14, which encode for NMIIB and NMIIC, respectively. To understand the role of myh genes in development, we obtained a null mutant for the myh9a gene and generated null mutants for the myh9b and myh10 genes using CRISPR/Cas genome editing. myh14 was not examined due to the low sequence homology. Through our studies we identified myh9b, not myh9a or myh10, as the critical myh gene required for normal zebrafish development and morphogenesis. Consistent with this finding, myh9a and myh10 homozygous mutants are viable through adulthood with no visible phenotypes. However, myh9b homozygous mutants are semi-lethal and develop pericardial edema between 48 and 96 hours post fertilization, a phenotype consistent with kidney dysfunction. This phenotype reverses shortly after onset, leading us to hypothesize that there is redundancy or compensation by other myh genes and proteins in these mutants. This is supported by the finding that double mutants display more severe phenotypes earlier in development than single mutants. In the human population there are five clinical disorders resulting from mutations in the MYH9 gene that are classified as MYH9-related disease (MYH9-RD), with many patients developing kidney dysfunction. Examination of larval myh9b homozygous mutant kidney structure revealed severe defects including podocyte foot process effacement, increased slit diaphragm size, and protein precipitate in Bowman’s space. These results suggest that myh9b mutants can be used as a model to study the development and progression of MYH9-RD. Current experiments are further investigating glomerular function and the cell type specific role for myh9b in development.