Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate
Ritva Rice, … , Irma Thesleff, David P.C. Rice
Ritva Rice, … , Irma Thesleff, David P.C. Rice
Published June 15, 2004
Citation Information: J Clin Invest. 2004;113(12):1692-1700. https://doi.org/10.1172/JCI20384.
View: Text | PDF
Article Development

Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate

Abstract

Classical research has suggested that early palate formation develops via epithelial-mesenchymal interactions, and in this study we reveal which signals control this process. Using Fgf10–/–, FGF receptor 2b–/– (Fgfr2b–/–), and Sonic hedgehog (Shh) mutant mice, which all exhibit cleft palate, we show that Shh is a downstream target of Fgf10/Fgfr2b signaling. Our results demonstrate that mesenchymal Fgf10 regulates the epithelial expression of Shh, which in turn signals back to the mesenchyme. This was confirmed by demonstrating that cell proliferation is decreased not only in the palatal epithelium but also in the mesenchyme of Fgfr2b–/– mice. These results reveal a new role for Fgf signaling in mammalian palate development. We show that coordinated epithelial-mesenchymal interactions are essential during the initial stages of palate development and require an Fgf-Shh signaling network.

Authors

Ritva Rice, Bradley Spencer-Dene, Elaine C. Connor, Amel Gritli-Linde, Andrew P. McMahon, Clive Dickson, Irma Thesleff, David P.C. Rice

×

Figure 4

Options: View larger image (or click on image) Download as PowerPoint
Detection of TUNEL-positive cells in the posterior oral cavity of WT, Fg...
Detection of TUNEL-positive cells in the posterior oral cavity of WT, Fgfr2b_/_, and Fgf10_/_ mice at E13. (A and D) TUNEL-positive cells were not detected in WT oral epithelium. (B, C, E, and F) TUNEL-positive cells were detected in the dorsum of the tongue (B and C, arrowheads), in the palatal bend (B, arrow), in the floor of the mouth (E, arrow), and in the MEE (F, arrow) in both Fgfr2b_/_ and Fgf10_/_ mice. TUNEL-positive cells were also occasionally detected in the palatal mesenchyme (B). D and F are high magnifications of the palatal shelf apex in A and C, respectively. A and C are the same magnification, as are B and E; scale bars: 100 ∝m.