Developmental activities of the complement pathway in migrating neurons

Gorelik, Anna , Sapir, Tamar , Haffner-Krausz, Rebecca , Olender, Tsviya , Woodruff, Trent M. and Reiner, Orly (2017) Developmental activities of the complement pathway in migrating neurons. Nature Communications, 8 15096 .1-15096 .12. doi:10.1038/ncomms15096


Author Gorelik, Anna
Sapir, Tamar
Haffner-Krausz, Rebecca
Olender, Tsviya
Woodruff, Trent M.
Reiner, Orly
Title Developmental activities of the complement pathway in migrating neurons
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2017-05-02
Sub-type Article (original research)
DOI 10.1038/ncomms15096
Open Access Status DOI
Volume 8
Start page 15096 .1
End page 15096 .12
Total pages 12
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
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.
Formatted 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.
Keyword Immune system
Brain diseases
C3
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
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Created: Thu, 01 Jun 2017, 09:41:41 EST by Dr Trent Woodruff on behalf of School of Biomedical Sciences