Developmental activities of the complement pathway in migrating neurons

Anna Gorelik, Tamar Sapir, Rebecca Haffner-Krausz, Tsviya Olender, Trent M. Woodruff and Orly Reiner ()
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Anna Gorelik: Weizmann Institute of Science
Tamar Sapir: Weizmann Institute of Science
Rebecca Haffner-Krausz: Weizmann Institute of Science
Tsviya Olender: Weizmann Institute of Science
Trent M. Woodruff: School of Biomedical Sciences, University of Queensland, BNE
Orly Reiner: Weizmann Institute of Science

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15096

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