title: Effects of Folic Acid and Homocysteine on the Morphogenesis of Mouse Cephalic Neural Crest Cells In Vitro.
abstract: Folate deficiency and hyperhomocysteinemia have long been associated with developmental anomalies, particularly neural tube defects and neurocristopathies-a group of diverse disorders that result from defective growth, differentiation, and migration of neural crest (NC) cells. However, the exact mechanisms by which homocysteine (Hcys) and/or folate deficiencies disrupt NC development are still poorly understood in mammals. In this work, we employed a well-defined culture system to investigate the effects of Hcys and folic acid (FA) supplementation on the morphogenetic processes of murine NC cells in vitro. We demonstrated that Hcys increases outgrowth and proliferation of cephalic NC cells and impairs their differentiation into smooth muscle cells. In addition, we showed that FA alone does not directly affect the developmental dynamics of the cephalic NC cells but is able to prevent the Hcys-induced effects. Our results, therefore, suggest that elevated Hcys levels per se cause dysmorphogenesis of the cephalic NC and might contribute to neurocristopathies in mammalian embryos.
authors.affiliation: Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis, SC, Brazil.
authors.forename: Fernanda Rosene
authors.initials: FR
authors.lastname: Melo
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Raul Bardini
authors.initials: RB
authors.lastname: Bressan
authors.affiliation: Department of Pediatrics, Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, United States.
authors.forename: Bruno
authors.initials: B
authors.lastname: Costa-Silva
authors.affiliation: Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianopolis, SC, Brazil. andrea.trentin@ufsc.br.
authors.forename: Andrea Gonçalves
authors.initials: AG
authors.lastname: Trentin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects / Q000196:embryology; D005492:Folic Acid / Q000008:administration & dosage*; D006710:Homocysteine / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000187:drug effects / Q000502:physiology*; D009432:Neural Crest / Q000187:drug effects / Q000196:embryology* / Q000502:physiology*
chemical_list: D006710:Homocysteine; D005492:Folic Acid
keywords: Folate deficiency; Hyperhomocysteinemia; Neural crest; Neurocristopathy; Smooth muscle