C5a receptor signaling prevents folate deficiency-induced neural tube defects in mice

J Immunol. 2013 Apr 1;190(7):3493-9. doi: 10.4049/jimmunol.1203072. Epub 2013 Feb 18.


The complement system is involved in a range of diverse developmental processes, including cell survival, growth, differentiation, and regeneration. However, little is known about the role of complement in embryogenesis. In this study, we demonstrate a novel role for the canonical complement 5a receptor (C5aR) in the development of the mammalian neural tube under conditions of maternal dietary folic acid deficiency. Specifically, we found C5aR and C5 to be expressed throughout the period of neurulation in wild-type mice and localized the expression to the cephalic regions of the developing neural tube. C5aR was also found to be expressed in the neuroepithelium of early human embryos. Ablation of the C5ar1 gene or the administration of a specific C5aR peptide antagonist to folic acid-deficient pregnant mice resulted in a high prevalence of severe anterior neural tube defect-associated congenital malformations. These findings provide a new and compelling insight into the role of the complement system during mammalian embryonic development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Complement C5 / genetics
  • Complement C5 / metabolism
  • Disease Models, Animal
  • Embryo, Mammalian / metabolism
  • Female
  • Folic Acid Deficiency / complications*
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Morphogenesis / genetics
  • Neural Tube / embryology
  • Neural Tube / metabolism
  • Neural Tube Defects / etiology*
  • Neural Tube Defects / pathology
  • Neural Tube Defects / prevention & control*
  • Neurulation / genetics
  • Pregnancy
  • Protein Transport
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Anaphylatoxin C5a / genetics
  • Receptor, Anaphylatoxin C5a / metabolism*
  • Signal Transduction*


  • Complement C5
  • RNA, Messenger
  • Receptor, Anaphylatoxin C5a