Cellular and Molecular Neurobiology

, Volume 37, Issue 2, pp 371–376 | Cite as

Effects of Folic Acid and Homocysteine on the Morphogenesis of Mouse Cephalic Neural Crest Cells In Vitro

  • Fernanda Rosene Melo
  • Raul Bardini Bressan
  • Bruno Costa-Silva
  • Andrea Gonçalves TrentinEmail author
Brief Communication


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.


Neural crest Neurocristopathy Hyperhomocysteinemia Folate deficiency Smooth muscle 



This work was supported by Ministério da Ciência, Tecnologia e Inovação/Conselho Nacional de Desenvolvimento Científico e Tecnológico (MCTI/CNPq/Brazil), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil), Instituto Nacional de Neurociência Translacional (MCTI/INNT), and Fundação de Amparo à Pesquisa do Estado de Santa Catarina (FAPESC, Brazil). RBB is supported by a fellowship from the Science Without Borders Program (CAPES, Brazil).

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Fernanda Rosene Melo
    • 1
  • Raul Bardini Bressan
    • 2
  • Bruno Costa-Silva
    • 3
  • Andrea Gonçalves Trentin
    • 1
    Email author
  1. 1.Department of Cell Biology, Embryology and GeneticsFederal University of Santa CatarinaFlorianopolisBrazil
  2. 2.MRC Centre for Regenerative MedicineUniversity of EdinburghEdinburghUK
  3. 3.Department of Pediatrics, Cell and Developmental BiologyWeill Cornell Medical CollegeNew YorkUnited States

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