Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development

Jose Henrique Ledo, Ran Zhang, Luka Mesin, Diego Mourão-Sá, Estefania P. Azevedo, Olga G. Troyanskaya, Victor Bustos, Paul Greengard

Research output: Contribution to journalArticle

Abstract

Microglial cells play a key role in brain homeostasis from development to adulthood. Here we show the involvement of a site-specific phosphorylation of Presenilin 1 (PS1) in microglial development. Profiles of microglia-specific transcripts in different temporal stages of development, combined with multiple systematic transcriptomic analysis and quantitative determination of microglia progenitors, indicate that the phosphorylation of PS1 at serine 367 is involved in the temporal dynamics of microglial development, specifically in the developing brain rudiment during embryonic microgliogenesis. We constructed a developing brain-specific microglial network to identify transcription factors linked to PS1 during development. Our data showed that PS1 functional connections appear through interaction hubs at Pu.1, Irf8 and Rela-p65 transcription factors. Finally, we showed that the total number of microglia progenitors was markedly reduced in the developing brain rudiment of embryos lacking PS1 phosphorylation compared to WT. Our work identifies a novel role for PS1 in microglial development.

Original languageEnglish (US)
Article numbere0237773
JournalPloS one
Volume15
Issue number8 August 2020
DOIs
StatePublished - Aug 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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