Chemokine signaling controls integrity of radial glial scaffold in developing spinal cord and consequential proper position of boundary cap cells

Yan Zhu, Tomoko Matsumoto, Takashi Nagasawa, Fabienne Mackay, Fujio Murakami

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

Radial glial cells are the neural progenitors of the developing CNS and have long radial processes that guide radially migrating neurons. The integrity of the radial glial scaffold, in particular proper adhesion between the endfeet of radial processes and the pial basement membrane (BM), is important for the cellular organization of the CNS, as indicated by evidence emerging from the developing cortex. However, the mechanisms underlying the maintenance of radial glial scaffold integrity during development, when the neuroepithelium rapidly expands, are still poorly understood. Here, we addressed this issue in the developing mouse spinal cord. We show that CXCR4, a receptor of chemokine CXCL12, is expressed in spinal cord radial glia. Conditional knock-out of Cxcr4 in radial glia caused disrupted radial glial scaffold with gaps at the pial endfeet layer and consequentially led to an invasion of boundary cap (BC) cells into the spinal cord. Because BC cells are PNS cells normally positioned at the incoming and outgoing axonal roots, their invasion into the spinal cord suggests a compromised CNS/PNS boundary in the absence of CXCL12/CXCR4 signaling. Both disrupted radial glial scaffold and invasion of BC cells into the CNS were also present in mice deficient in CXCR7, a second receptor of CXCL12. We further show that CXCL12 signaling promotes the radial glia adhesion to BM components and activates integrin β1 avidity. Our study unravels a novel molecular mechanism that deploys CXCL12/CXCR4/CXCR7 for the maintenance of radial glial scaffold integrity, which in turn safeguards the CNS/PNS boundary during spinal cord development.

Original languageEnglish
Pages (from-to)9211-9224
Number of pages14
JournalJournal of Neuroscience
Volume35
Issue number24
DOIs
Publication statusPublished - 17 Jun 2015

Keywords

  • Boundary cap cells
  • CXCL12
  • CXCR4
  • Integrin b1
  • Pial endfeet
  • Radial glia

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