Gurjoth S. J. Deol, Tina N. Cuthbert, Mohamed I. Gatie, Danielle M. Spice, Lindsay R. Hilton, Gregory M. Kelly
Abstract
Mouse F9 cells differentiate into primitive extraembryonic endoderm (PrE) when treated with retinoic acid (RA), and this is accompanied by an up-regulation of Gata6. The role of the GATA6 network in PrE differentiation is known, and we have shown it directly activates Wnt6. Canonical Wnt/β-catenin signaling is required by F9 cells to differentiate to PrE, and this, like most developmental processes, requires input from one or more additional pathways. We found both RA and Gata6 overexpression, can induce the expression of Indian Hedgehog (Ihh) and a subset of its target genes through Gli activation during PrE induction. Chemical activation of the Hh pathway using a Smoothened agonist (SAG) also increased Gli reporter activity, and as expected, when Hh signaling was blocked with a Smoothened antagonist, cyclopamine, this RA-induced reporter activity was reduced. Interestingly, SAG alone failed to induce markers of PrE differentiation, and had no effect on Wnt/β-catenin-dependent TCF-LEF reporter activity. The expected increase in Wnt/β-catenin-dependent TCF-LEF reporter activity and PrE markers induced by RA was, however, blocked by cyclopamine. Finally, inhibiting GSK3 activity with BIO increased both TCF-LEF and Gli reporter activities. Together, we demonstrate the involvement of Hh signaling in the RA-induced differentiation of F9 cells into PrE, and while the activation of the Hh pathway itself is not sufficient, it as well as active Wnt/β-catenin are necessary for F9 cell differentiation.
Pharmacology, Toxicology and Pharmaceutical Science
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7%
Other
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 November 2017.
All research outputs
#6,969,850
of 23,005,189 outputs
Outputs from Frontiers in Cell and Developmental Biology
#1,589
of 9,115 outputs
Outputs of similar age
#114,143
of 327,861 outputs
Outputs of similar age from Frontiers in Cell and Developmental Biology
#5
of 26 outputs
Altmetric has tracked 23,005,189 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 9,115 research outputs from this source. They receive a mean Attention Score of 3.4. This one has done well, scoring higher than 82% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 327,861 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.
We're also able to compare this research output to 26 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.
