PUBLICATION

Il34-Csf1r Pathway Regulates the Migration and Colonization of Microglial Precursors

Authors
Wu, S., Xue, R., Hassan, S., Nguyen, T.M.L., Wang, T., Pan, H., Xu, J., Liu, Q., Zhang, W., Wen, Z.
ID
ZDB-PUB-180913-20
Date
2018
Source
Developmental Cell   46: 552-563.e4 (Journal)
Registered Authors
Wen, Zilong
Keywords
Csf1r, Il34, colonization, microglia, migration, neuronal apoptosis, zebrafish
MeSH Terms
  • Animals
  • Apoptosis
  • Brain/cytology
  • Brain/physiology*
  • Cell Differentiation
  • Cell Movement*
  • Embryonic Development
  • Interleukins/genetics
  • Interleukins/metabolism*
  • Microglia/cytology
  • Microglia/physiology*
  • Neurons/cytology
  • Neurons/physiology*
  • Receptors, Colony-Stimulating Factor/genetics
  • Receptors, Colony-Stimulating Factor/metabolism*
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
PubMed
30205037 Full text @ Dev. Cell
Abstract
Microglia are the major immune cells in the central nervous system (CNS). Born in peripheral hematopoietic tissues, microglial precursors colonize the CNS during early embryogenesis and maintain themselves thereafter. However, the mechanism underlying this colonization process remains elusive. We have recently demonstrated that neuronal apoptosis contributes to microglia colonization in zebrafish. Here, we further show that prior to neuronal apoptosis, microglial precursors are attracted to the proximal brain regions by brain-derived interleukin 34 (il34) and its receptor colony-stimulating factor 1 receptor a (csf1ra). In both il34- and csf1ra-deficient zebrafish larva, embryonic macrophages fail to migrate to the anterior head and colonize the CNS, but their initial development and colonization to peripheral tissues remain largely unaffected. Activation of Il34-Csf1ra pathway is sufficient to attract embryonic macrophages to the CNS independent of neuronal apoptosis. Our study shows that cytokine signaling and neuronal apoptosis synergistically orchestrate the colonization of microglia in early zebrafish development.
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