Developmental Activities of the Complement Pathway in Migrating Neurons

Nat Commun. 2017 May 2;8:15096. doi: 10.1038/ncomms15096.

Abstract

In recent years the notion that malfunctioning of the immune system may result in developmental brain diseases has emerged. However, the role of immune molecules in the developing brain has not been well explored. The complement pathway converges to cleave C3. Here we show that key proteins in the lectin arm of this pathway, MASP1, MASP2 and C3, are expressed in the developing cortex and that neuronal migration is impaired in knockout and knockdown mice. Molecular mimics of C3 cleavage products rescue the migration defects that have been seen following knockdown of C3 or Masp2. Pharmacological activation of the downstream receptors rescue Masp2 and C3 knockdown as well as C3 knockout. Therefore, we propose that the complement pathway is functionally important in migrating neurons of the developing cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / immunology
  • Complement C3 / antagonists & inhibitors
  • Complement C3 / genetics*
  • Complement C3 / immunology
  • Complement Pathway, Mannose-Binding Lectin / genetics*
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental / immunology*
  • Male
  • Mannose-Binding Protein-Associated Serine Proteases / antagonists & inhibitors
  • Mannose-Binding Protein-Associated Serine Proteases / genetics*
  • Mannose-Binding Protein-Associated Serine Proteases / immunology
  • Mice
  • Mice, Knockout
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / immunology*
  • Oligopeptides / pharmacology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptor, Anaphylatoxin C5a / agonists
  • Receptor, Anaphylatoxin C5a / genetics
  • Receptor, Anaphylatoxin C5a / immunology
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / immunology
  • Signal Transduction

Substances

  • C3a-derived anaphylatoxin receptor, mouse
  • C5ar1 protein, mouse
  • Complement C3
  • Oligopeptides
  • RNA, Small Interfering
  • Receptor, Anaphylatoxin C5a
  • Receptors, G-Protein-Coupled
  • MASP-1 protein, mouse
  • MASP-2 protein, mouse
  • Mannose-Binding Protein-Associated Serine Proteases