Analysis of Cardiac Teratogenicity of Phenylalanine Using the Avian Model: the Role of the Focal Adhesion Pathway

Abstract

Maternal phenylketonuria (MPKU) is characterized by the teratogenic effects of phenylalanine (Phe). High levels of intrauterine Phe cause cardiovascular malformations (CVMs), intellectual impairment, microcephaly, and low gestation mass. Mothers with PKU must maintain a strict diet to insure serum Phe concentrations remain below 360 µM to avoid these congenital defects. Previous functional genomic studies from our lab have determined the importance of the focal adhesion pathway (FAP) in the development of heart defects caused by MPKU. Our project aims to visualize mRNA expression during stages HH10-14 in chicken embryos using in-situ Hybridization (ISH). This will allow us to qualitatively assess the expression of genes associated with the FAP in heart and out flow tract (OFT) tissue. Hepatocyte growth factor, the ligand for c-MET tyrosine kinase receptor is one of six genes we identified and has been shown to promote angiogenesis. Also, other in-situ Hybridization studies have shown that HGF is present in the pharyngeal region of developing embryos. Our project goal is to characterize expression domains for all six differentially expressed FAP genes in Phe treated embryos.