PgmNr Z6058: The role of TGFβ member Gdf3 in left-right patterning.

Authors:
J. Pelliccia; R. Burdine


Institutes
Princeton University, Princeton, NJ.


Abstract:

The proper placement of organs in vertebrates is dependent on the expression of nodal  in the left lateral plate mesoderm (LPM). For this to occur in zebrafish, the expression of the nodal ortholog spaw needs to be activated in the left LPM and inhibited in the right LPM. Bilateral expression of nodal (i.e. expression in both the left and right LPM) or expression in the right LPM leads to aberrant organ placement.  We have focused on understanding the role of Gdf3 in the proper expression of spaw. Gdf3 is a TGFbeta ligand whose mRNA is present during the stages of mesoderm and endoderm patterning and during the stages of left-right patterning in zebrafish embryonic development. Using morpholinos against gdf3, we have identified a dual role of gdf3 in left-right patterning. Both in the expression of spaw and in the proper development of the laterality organ in zebrafish called Kupffer's vesicle (KV). Our data suggest that gdf3 is required for proper temporal expression of spaw in the lateral plate mesoderm and for the proper asymmetric expression of dand5, a spaw inhibitor needed to prevent spaw expression in the right lateral plate mesoderm. The aberrant development of KV in these gdf3 morphants was likely the cause of the irregular expression of dand5.  Additionally, our attempts at making mutants using CRISPR/Cas9 technology have been rewarded with potential gdf3 zebrafish mutants that exhibit defects in mesoderm and endoderm formation. These defects are also attributed to previously identified mutations in two other nodal orthologs called cyclops and squint.  Collectively, our initial findings indicate that gdf3 is important for mesoderm and endoderm patterning in early development and it may then be subsequently required for proper left-right patterning .



ZFIN Genetics Index
1. spaw
2. dand5
3. gdf3