The tbx5a mutant, heartstrings, has a lethal phenotype where the primary heart tube fails to loop during development and a pectoral fin is not formed. Our lab group has previously shown that cells within the anterior lateral plate mesoderm fail to converge in Tbx5a knockdown conditions during limb initiation. We have hypothesized that during limb initiation, Tbx5a may play an early role in the ability of lateral plate mesoderm to migrate towards a localized signaling source of an Fgf molecule, namely Fgf24.
We have further elucidated a fate map for the Tbx5a-positive cells of the lateral plate mesoderm to include the heart tissues and have studied the dynamics of cardiac precursor migration using timelapse imaging. One interesting facet of this study is that the formation of the heart occurs asymmetrically, with looping of the heart tube towards the left side. We will report upon the specification and migration of the lateral plate mesoderm on the right versus left sides of the wild-type embryo during heart formation. Here we will also address whether cardiac precursors migrate topologically in a manner similar to limb bud precursors, or if the migration dynamics of the heart precursors are significantly different to those of the limb bud precursors.
Studying the dynamics of the migration in this process has generated several questions: Does Tbx5a have a similar early migration function in other systems such as cardiac precursors? Do similar ligand-receptor interactions found to play important roles during limb bud development also occur during the migration of heart precursors? Alternatively, could Tbx5a be affecting cell fate decisions within the anterior lateral plate mesoderm? To address these issues, we will also report upon the specification and migration of the lateral plate mesoderm precursors in Tbx5a knockdown embryos compared to wild-type embryos.