Developmental Apoptosis Promotes a Disease-Related Gene Signature and Independence from CSF1R Signaling in Retinal Microglia

Cell Rep. 2019 May 14;27(7):2002-2013.e5. doi: 10.1016/j.celrep.2019.04.062.


Microglia have important remodeling functions in neurodevelopment, aging, and disease, with evidence for molecular diversity. However, the signaling pathways and environmental cues that drive diverse states of microglia are incompletely understood. We profiled microglia of a discrete developing CNS region, the murine retina. We found distinct transcriptional signatures for retinal microglia across development and peak postnatal density of a population that resembles aging and disease-associated microglia (DAM) and CD11c+ microglia of developing white matter. While TREM2 signaling modulates the expression of select genes, the DAM-related signature is significantly reduced in retinas lacking Bax, a proapoptotic factor required for neuronal death. Furthermore, we found postnatal retinal microglia highly expressing CD11c are resistant to loss or inhibition of colony stimulating factor 1 receptor (CSF1R), while most microglia can be eliminated in Bax knockout retina. Thus, developmental apoptosis promotes a microglia gene signature linked to CSF1R independence that shares features with microglia in developing white matter and in disease.

Keywords: apoptosis; development; disease-associated; microglia; retina; transcriptome.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Differentiation*
  • Mice
  • Mice, Knockout
  • Microglia / metabolism*
  • Microglia / pathology
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Diseases / genetics
  • Retinal Diseases / metabolism*
  • Retinal Diseases / pathology
  • Signal Transduction*
  • Transcriptome*


  • Csf1r protein, mouse
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor