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

First Author  Ledo JH Year  2020
Journal  PLoS One Volume  15
Issue  8 Pages  e0237773
PubMed ID  32822378 Mgi Jnum  J:293899
Mgi Id  MGI:6452363 Doi  10.1371/journal.pone.0237773
Citation  Ledo JH, et al. (2020) Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development. PLoS One 15(8):e0237773
abstractText  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.
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