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

TitleLack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development.
Publication TypeJournal Article
Year of Publication2020
AuthorsLedo, JHenrique, Zhang, R, Mesin, L, Mourão-Sá, D, Azevedo, EP, Troyanskaya, OG, Bustos, V, Greengard, P
JournalPLoS One
Volume15
Issue8
Paginatione0237773
Date Published2020
ISSN1932-6203
KeywordsAnimals, Brain, Female, Gene Regulatory Networks, Male, Mice, Inbred C57BL, Microglia, Phosphorylation, Presenilin-1, Stem Cells, Transcriptome
Abstract

<p>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.</p>

DOI10.1371/journal.pone.0237773
Alternate JournalPLoS One
PubMed ID32822378
PubMed Central IDPMC7444478
Grant ListR01 AG019770 / AG / NIA NIH HHS / United States
R01 GM071966 / GM / NIGMS NIH HHS / United States