PMID- 28947813
OWN - NLM
STAT- MEDLINE
DCOM- 20190716
LR  - 20190716
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Sep 25
TI  - ICM conversion to epiblast by FGF/ERK inhibition is limited in time and requires 
      transcription and protein degradation.
PG  - 12285
LID - 10.1038/s41598-017-12120-0 [doi]
LID - 12285
AB  - Inner cell Mass (ICM) specification into epiblast (Epi) and primitive endoderm 
      (PrE) is an asynchronous and progressive process taking place between E3.0 to 
      E3.75 under the control of the Fibroblast Growth Factor (FGF)/Extracellular 
      signal-Regulated Kinase (ERK) signaling pathway. Here, we have analyzed in 
      details the kinetics of specification and found that ICM cell responsiveness to 
      the up and down regulation of FGF signaling activity are temporally distinct. We 
      also showed that PrE progenitors are generated later than Epi progenitors. We 
      further demonstrated that, during this late phase of specification, a 4 hours 
      period of FGF/ERK inhibition prior E3.75 is sufficient to convert ICM cells into 
      Epi. Finally, we showed that ICM conversion into Epi in response to inhibition 
      during this short time window requires both transcription and proteasome 
      degradation. Collectively, our data give new insights into the timing and 
      mechanisms involved in the process of ICM specification.
FAU - Bessonnard, Sylvain
AU  - Bessonnard S
AD  - Institut Pasteur, CNRS, Unite de Genetique Fonctionnelle de la Souris, UMR 3738, 
      Department of Developmental & Stem Cell Biology, 25 rue du docteur Roux, F-75015, 
      Paris, France.
FAU - Coqueran, Sabrina
AU  - Coqueran S
AD  - Institut Pasteur, CNRS, Unite de Genetique Fonctionnelle de la Souris, UMR 3738, 
      Department of Developmental & Stem Cell Biology, 25 rue du docteur Roux, F-75015, 
      Paris, France.
FAU - Vandormael-Pournin, Sandrine
AU  - Vandormael-Pournin S
AD  - Institut Pasteur, CNRS, Unite de Genetique Fonctionnelle de la Souris, UMR 3738, 
      Department of Developmental & Stem Cell Biology, 25 rue du docteur Roux, F-75015, 
      Paris, France.
FAU - Dufour, Alexandre
AU  - Dufour A
AUID- ORCID: 0000-0002-9417-7389
AD  - Institut Pasteur, Bioimage Analysis Unit, CNRS UMR 3691, Paris, France.
AD  - INSERM UMR935, Paul Brousse Hospital, University Paris Sud, Villejuif, France.
FAU - Artus, Jerome
AU  - Artus J
AD  - Institut Pasteur, CNRS, Unite de Genetique Fonctionnelle de la Souris, UMR 3738, 
      Department of Developmental & Stem Cell Biology, 25 rue du docteur Roux, F-75015, 
      Paris, France. jerome.artus@u-psud.fr.
AD  - INSERM UMR935, Paul Brousse Hospital, University Paris Sud, Villejuif, France. 
      jerome.artus@u-psud.fr.
AD  - Faculty of Medicine, Kremlin-Bicetre, University Paris Sud, Paris Saclay, France. 
      jerome.artus@u-psud.fr.
FAU - Cohen-Tannoudji, Michel
AU  - Cohen-Tannoudji M
AUID- ORCID: 0000-0002-6405-2657
AD  - Institut Pasteur, CNRS, Unite de Genetique Fonctionnelle de la Souris, UMR 3738, 
      Department of Developmental & Stem Cell Biology, 25 rue du docteur Roux, F-75015, 
      Paris, France. m-cohen@pasteur.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170925
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - Animals
MH  - Blastocyst Inner Cell Mass/*physiology
MH  - Cell Differentiation/*physiology
MH  - Cell Plasticity/physiology
MH  - Fibroblast Growth Factors/*metabolism
MH  - Germ Layers/*physiology
MH  - MAP Kinase Signaling System/*physiology
MH  - Mice
MH  - Proteolysis
MH  - Time Factors
MH  - Transcription, Genetic/physiology
PMC - PMC5612930
COIS- The authors declare that they have no competing interests.
EDAT- 2017/09/28 06:00
MHDA- 2019/07/17 06:00
PMCR- 2017/09/25
CRDT- 2017/09/27 06:00
PHST- 2017/06/19 00:00 [received]
PHST- 2017/09/04 00:00 [accepted]
PHST- 2017/09/27 06:00 [entrez]
PHST- 2017/09/28 06:00 [pubmed]
PHST- 2019/07/17 06:00 [medline]
PHST- 2017/09/25 00:00 [pmc-release]
AID - 10.1038/s41598-017-12120-0 [pii]
AID - 12120 [pii]
AID - 10.1038/s41598-017-12120-0 [doi]
PST - epublish
SO  - Sci Rep. 2017 Sep 25;7(1):12285. doi: 10.1038/s41598-017-12120-0.