Publication

Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways

Kierdorf, K., Erny, D., Goldmann, T., Sander, V., Schulz, C., Perdiguero, E. G., Wieghofer, P., Heinrich, A., Riemke, P., Hoelscher, C., Mueller, D. N., Luckow, B., Brocker, T., Debowski, K., Fritz, G., Opdenakker, G., Diefenbach, A., Biber, K., Heikenwalder, M., Geissmann, F., Rosenbauer, F. & Prinz, M., Mar-2013, In : Nature neuroscience. 16, 3, p. 273-280 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Katrin Kierdorf
  • Daniel Erny
  • Tobias Goldmann
  • Victor Sander
  • Christian Schulz
  • Elisa Gomez Perdiguero
  • Peter Wieghofer
  • Annette Heinrich
  • Pia Riemke
  • Christoph Hoelscher
  • Dominik N. Mueller
  • Bruno Luckow
  • Thomas Brocker
  • Katharina Debowski
  • Guenter Fritz
  • Ghislain Opdenakker
  • Andreas Diefenbach
  • Knut Biber
  • Mathias Heikenwalder
  • Frederic Geissmann
  • Frank Rosenbauer
  • Marco Prinz

Microglia are crucial for immune responses in the brain. Although their origin from the yolk sac has been recognized for some time, their precise precursors and the transcription program that is used are not known. We found that mouse microglia were derived from primitive c-kit(+) erythromyeloid precursors that were detected in the yolk sac as early as 8 d post conception. These precursors developed into CD45(+) c-kit(lo) CX(3)CR1(-) immature (A1) cells and matured into CD45(+) c-kit(-) CX(3)CR1(+) (A2) cells, as evidenced by the downregulation of CD31 and concomitant upregulation of F4/80 and macrophage colony stimulating factor receptor (MCSF-R). Proliferating A2 cells became microglia and invaded the developing brain using specific matrix metalloproteinases. Notably, microgliogenesis was not only dependent on the transcription factor Pu.1 (also known as Sfpi), but also required Irf8, which was vital for the development of the A2 population, whereas Myb, Id2, Batf3 and Klf4 were not required. Our data provide cellular and molecular insights into the origin and development of microglia.

Original languageEnglish
Pages (from-to)273-280
Number of pages8
JournalNature neuroscience
Volume16
Issue number3
Publication statusPublished - Mar-2013

    Keywords

  • YOLK-SAC, TRANSCRIPTION FACTORS, FRACTALKINE RECEPTOR, DENDRITIC CELLS, MYELOID CELLS, MACROPHAGES, BRAIN, DIFFERENTIATION, HETEROGENEITY, PROGENITORS

ID: 5801676