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Folic acid and homocysteine affect neural crest and neuroepithelial cell outgrowth and differentiation in vitro
Author(s) -
Boot Marit J.,
SteegersTheunissen Régine P.M.,
Poelmann Robert E.,
Van Iperen Liesbeth,
Lindemans Jan,
GittenbergerDe Groot Adriana C.
Publication year - 2003
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.10303
Subject(s) - neuroepithelial cell , neural tube , neural crest , neurulation , neural fold , biology , neural plate , microbiology and biotechnology , homocysteine , medicine , endocrinology , anatomy , neural stem cell , embryo , embryogenesis , stem cell , gastrulation
The beneficial effect of additional folic acid in the periconceptional period to prevent neural tube defects, orofacial clefts, and conotruncal heart defects in the offspring has been shown. Folate shortage results in homocysteine accumulation. Elevated levels of homocysteine have been related to neural tube defects. We studied the behavior of neuroepithelial cells and cranial and cardiac neural crest cells in vitro. Neural tube explants were cultured for 24 and 48 hr in medium after addition of folic acid and/or homocysteine. Folic acid addition increased neuroepithelial cell outgrowth and increased neural crest cell differentiation into nerve and smooth muscle cells. Addition of homocysteine increased neural crest cell outgrowth and migration from the neural tube and inhibited neural crest cell differentiation. Our findings suggest that neural tube defects caused by folate deficiency and hyperhomocysteinemia develop due to increased neuroepithelial to neural crest cell transformation. This increased transformation leads to a shortage of neuroepithelial cells in the neural tube. Defects in orofacial and conotruncal development are explained by abnormal differentiation of neural crest cells in the presence of high homocysteine concentrations. Our findings supports a critical role for folic acid and homocysteine in the development of neural tube defects and neural crest related heart malformations. Developmental Dynamics 227:301–308, 2003. © 2003 Wiley‐Liss, Inc.