Microarray analysis of homocysteine‐responsive genes in cardiac neural crest cells in vitro

• Published in: Developmental dynamics Vol. 236; no. 4; pp. 1044 - 1054
• Main Authors: Rosenquist, T.H., Bennett, G.D., Brauer, P.R., Stewart, M.L., Chaudoin, T.R., Finnell, R.H.
• Format: Journal Article
• Language: English
• Published: New York Wiley‐Liss, Inc 01.04.2007
• Subjects: Animals; Cell Adhesion - drug effects; Cell Adhesion - genetics; Cell Movement - drug effects; Cell Movement - genetics; Cells, Cultured; Chick Embryo; embryo; expression profiling; Gene Expression Profiling; Gene Expression Regulation, Developmental - drug effects; homocysteine; Homocysteine - pharmacology; microarray; Myoblasts, Cardiac - metabolism; neural crest; Neural Crest - embryology; Neural Crest - metabolism; Oligonucleotide Array Sequence Analysis
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.21101

The amino acid homocysteine increases in the serum when there is insufficient folic acid or vitamin B12, or with certain mutations in enzymes important in methionine metabolism. Elevated homocysteine is related to increased risk for cardiovascular and other diseases in adults and elevated maternal homocysteine increases the risk for certain congenital defects, especially those that result from abnormal development of the neural crest and neural tube. Experiments with the avian embryo model have shown that elevated homocysteine perturbs neural crest/neural tube migration in vitro and in vivo. Whereas there have been numerous studies of homocysteine‐induced changes in gene expression in adult cells, there is no previous report of a homocysteine‐responsive transcriptome in the embryonic neural crest. We treated neural crest cells in vitro with exogenous homocysteine in a protocol that induces significant changes in neural crest cell migration. We used microarray analysis and expression profiling to identify 65 transcripts of genes of known function that were altered by homocysteine. The largest set of effected genes (19) included those with a role in cell migration and adhesion. Other major groups were genes involved in metabolism (13); DNA/RNA interaction (11); cell proliferation/apoptosis (10); and transporter/receptor (6). Although the genes identified in this experiment were consistent with prior observations of the effect of homocysteine upon neural crest cell function, none had been identified previously as response to homocysteine in adult cells. Developmental Dynamics 236:1044–1054, 2007. © 2007 Wiley‐Liss, Inc.