Wnt11/Fgfr1b cross-talk modulates the fate of cells in palate development

Abstract

Various cellular and molecular events underlie the elevation and fusion of the developing palate that occurs during embryonic development. This includes convergent extension, where the medial edge epithelium is intercalated into the midline epithelial seam. We examined the expression patterns of Wnt11 and Fgfr1b - which are believed to be key factors in convergent extension - in mouse palate development. Wnt-11 overexpression and beads soaked in SU5402 (an Fgfr1 inhibitor) were employed in in vitro organ cultures. The results suggested that interactions between Wnt11 and Fgfr1b are important in modulating cellular events such as cell proliferation for growth and apoptosis for fusion. Moreover, the Wnt11 siRNA results showed that Wnt11-induced apoptosis was necessary for palatal fusion. In summary, Fgfr1b induces cell proliferation in the developing palate mesenchyme so that the palate grows and contacts each palatal shelf, with negative feedback of Fgfs triggered by excessive cell proliferation then inhibiting the expression of Fgfr1b and activating the expression of Wnt11 to fuse each palate by activating apoptosis.

Evidence for the involvement of Fibroblast Growth Factor 10 in lipofibroblast formation during embryonic lung development

“…However, Fgf10 also binds with high affinity to Fgfr1b (Ornitz et al, 1996), which is expressed by both the epithelium and the mesenchyme (Lee et al, 2008). In the early developing mouse lung, it is well accepted that mesenchymal Fgf10 acts on the epithelium through its receptor Fgfr2b, whereas a direct action on the mesenchyme does not occur until E14.5 (De Langhe et al, 2006).…”

Mechanisms of tissue fusion during development

“…Some MEE cells also migrate away from the midline, where first contact occurs, towards the oral and nasal cavities along the MES to areas termed the 'epithelial triangles' (Martinez-Alvarez et al, 2000). As fusion continues and the epithelial layer is disrupted, mesenchymal cells from both shelves infiltrate the MES to establish continuity between the two tissues (Farbman, 1968;Hinrichsen and Stevens, 1974;Lee et al, 2008).…”

“…In addition, signaling through the WNT pathway is implicated in palatal fusion, as mice that are homozygous null for two WNT receptors, frizzled 1 (Fzd1) and frizzled 2 (Fzd2), have completely penetrant CP (Yu et al, 2010). Wnt11 is expressed in the MEE during fusion and is required for fusion of palatal shelves, as siRNA knockdown of Wnt11 in vitro results in decreased apoptosis in MEE cells and failure of fusion (Lee et al, 2008). Retinoic acid (RA) signaling in neural-crest-derived mesenchyme also must be tightly controlled, as either too little or too much RA causes CP (Lohnes et al, 1994;Cuervo et al, 2002).…”

Divergent roles for Wnt/β-catenin signaling in epithelial maintenance and breakdown during semicircular canal formation

“…The Wnt signaling pathway has been implicated in the fusion of several other tissues, including the neural tube, palate and ventricular septum (Pinson et al, 2000;Lee et al, 2008;Song et al, 2009;Song et al, 2010;Yu et al, 2012). However, a unifying theory for how Wnt signaling functions to mediate tissue fusion has yet to be elucidated and might very well be context dependent.…”