Ras-dva1 small GTPase regulates telencephalon development in Xenopus laevis embryos by controlling Fgf8 and Agr signaling at the anterior border of the neural plate

We previously found that the small GTPase Ras-dva1 is essential for the telencephalic development in Xenopus laevis because Ras-dva1 controls the Fgf8-mediated induction of FoxG1 expression, a key telencephalic regulator. In this report, we show, however, that Ras-dva1 and FoxG1 are expressed in dif...

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Bibliographic Details
Published in:Biology open 2014-03, Vol.3 (3), p.192-203
Main Authors: Tereshina, Maria B, Ermakova, Galina V, Ivanova, Anastasiya S, Zaraisky, Andrey G
Format: Article
Language:English
Subjects:
Agr
Anterior neural border
Control theory
Embryos
Feedback
Feedback loops
Fgf8
Fibroblast growth factor 8
Forebrain development
FoxG1
Foxg1 protein
Homeobox
Neural plate
Otx2
Otx2 protein
Ras-dva
Signal transduction
Signaling
Telencephalon
Xenopus laevis
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Summary:We previously found that the small GTPase Ras-dva1 is essential for the telencephalic development in Xenopus laevis because Ras-dva1 controls the Fgf8-mediated induction of FoxG1 expression, a key telencephalic regulator. In this report, we show, however, that Ras-dva1 and FoxG1 are expressed in different groups of cells; whereas Ras-dva1 is expressed in the outer layer of the anterior neural fold, FoxG1 and Fgf8 are activated in the inner layer from which the telencephalon is derived. We resolve this paradox by demonstrating that Ras-dva1 is involved in the transduction of Fgf8 signal received by cells in the outer layer, which in turn send a feedback signal that stimulates FoxG1 expression in the inner layer. We show that this feedback signal is transmitted by secreted Agr proteins, the expression of which is activated in the outer layer by mediation of Ras-dva1 and the homeodomain transcription factor Otx2. In turn, Agrs are essential for maintaining Fgf8 and FoxG1 expression in cells at the anterior neural plate border. Our finding reveals a novel feedback loop mechanism based on the exchange of Fgf8 and Agr signaling between neural and non-neural compartments at the anterior margin of the neural plate and demonstrates a key role of Ras-dva1 in this mechanism.
ISSN:2046-6390
2046-6390
DOI:10.1242/bio.20147401