Heart malformations are the most frequent cause of infant mortality resulting from congenital defects, and late heart morphogenetic events that serve to form the multi-chambered organ will not occur without proper looping of the early heart tube. During gastrulation in Xenopus laevis, patterning of the heart promordia is dependent on heparan sulfate proteoglycans (HSPGs) on the surface of the non-cardiac animal cap ectoderm, where two members of a major class of transmembrane HSPGs known as the syndecans are exclusively expressed.
The aims of this research are to define the role of syndecans in heart development, identify the cell lineages and molecular mechanisms by which syndecans function, and establish where syndecans are in the pathway for left-right induction of heart development. In Heart mesoderm, induction and left- right orientation will be evaluated morphologically and with molecular markers. In specific cell lineages, over-expression of syndecan constructions that lack domains known to be critical for their function will define the molecular role of syndecans in heart development. Finally, the position of syndecans within an established left-right signaling pathway will be determined by performing early molecular and embryological manipulations known to affect left-right development and evaluating their effect on syndecan expression.
