Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development.
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...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2020-01-01
|
Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0237773 |
id |
doaj-d4ab345b9e074e9b86f224c51554c19b |
---|---|
record_format |
Article |
spelling |
doaj-d4ab345b9e074e9b86f224c51554c19b2021-03-04T13:08:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01158e023777310.1371/journal.pone.0237773Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development.Jose Henrique LedoRan ZhangLuka MesinDiego Mourão-SáEstefania P AzevedoOlga G TroyanskayaVictor BustosPaul GreengardMicroglial 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.https://doi.org/10.1371/journal.pone.0237773 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jose Henrique Ledo Ran Zhang Luka Mesin Diego Mourão-Sá Estefania P Azevedo Olga G Troyanskaya Victor Bustos Paul Greengard |
spellingShingle |
Jose Henrique Ledo Ran Zhang Luka Mesin Diego Mourão-Sá Estefania P Azevedo Olga G Troyanskaya Victor Bustos Paul Greengard Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development. PLoS ONE |
author_facet |
Jose Henrique Ledo Ran Zhang Luka Mesin Diego Mourão-Sá Estefania P Azevedo Olga G Troyanskaya Victor Bustos Paul Greengard |
author_sort |
Jose Henrique Ledo |
title |
Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development. |
title_short |
Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development. |
title_full |
Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development. |
title_fullStr |
Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development. |
title_full_unstemmed |
Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development. |
title_sort |
lack of a site-specific phosphorylation of presenilin 1 disrupts microglial gene networks and progenitors during development. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.pone.0237773 |
work_keys_str_mv |
AT josehenriqueledo lackofasitespecificphosphorylationofpresenilin1disruptsmicroglialgenenetworksandprogenitorsduringdevelopment AT ranzhang lackofasitespecificphosphorylationofpresenilin1disruptsmicroglialgenenetworksandprogenitorsduringdevelopment AT lukamesin lackofasitespecificphosphorylationofpresenilin1disruptsmicroglialgenenetworksandprogenitorsduringdevelopment AT diegomouraosa lackofasitespecificphosphorylationofpresenilin1disruptsmicroglialgenenetworksandprogenitorsduringdevelopment AT estefaniapazevedo lackofasitespecificphosphorylationofpresenilin1disruptsmicroglialgenenetworksandprogenitorsduringdevelopment AT olgagtroyanskaya lackofasitespecificphosphorylationofpresenilin1disruptsmicroglialgenenetworksandprogenitorsduringdevelopment AT victorbustos lackofasitespecificphosphorylationofpresenilin1disruptsmicroglialgenenetworksandprogenitorsduringdevelopment AT paulgreengard lackofasitespecificphosphorylationofpresenilin1disruptsmicroglialgenenetworksandprogenitorsduringdevelopment |
_version_ |
1714800651411652608 |