Developmental activities of the complement pathway in migrating neurons

Anna Gorelik; Tamar Sapir; Rebecca Haffner-Krausz; Tsviya Olender; Trent M Woodruff; Orly Reiner

doi:10.1038/ncomms15096

Developmental activities of the complement pathway in migrating neurons

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

Authors

Anna Gorelik¹, Tamar Sapir¹, Rebecca Haffner-Krausz², Tsviya Olender¹, Trent M Woodruff³, Orly Reiner¹

Affiliations

¹ Department of Molecular Genetics, Weizmann Institute of Science, 234 Herzl St, Rehovot 7610001, Israel.
² Department of Veterinary Resources, Weizmann Institute of Science, 234 Herzl St, Rehovot 7610001, Israel.
³ School of Biomedical Sciences, University of Queensland, BNE, Brisbane, Queensland 4072, Australia.

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