Figure 6

Schematic diagram drawn after Mailleux et al, 2001, ofFibroblast growth factor 10(Fgf10) and murineSprouty2(mSpry2) expression respectively adjacent to and within the epithlium of an epithelial branch tip in the periphery of an early embryonic mouse lung. In panel a., Fgf10 is beginning to be expressed in the mesenchyme at a point where a bud is about to arise. Note that there is a gap between the epithelium and the locus of Fgf10 expression. At that time mSpry2 is either not expressed or is expressed at low levels. In panel b., an epithelial bud has begun to arise and is moving towards the chemoattractive source of FGF10 located in the mesenchyme near the adjacent pleura. At this time mSpry2 expression is increasing within the distal epithelial tip. In panel c., the bud has extended to a point close to where it will begin to branch. The Fgf10 expression domain is beginning to spread out towards the sides of the tip and mSpry2 is expressed at a high level. In panel d., the bud is extending into the Fgf10 expression domain, which has by now thinned between the bud tip and the adjacent pleura and extends downwards on either side of the bud tip between it and the adjacent bud tips (not shown). The level of mSpry2 expression within the bud tip epithelium is now high and the bud has stopped extending and is about to split. In panel e., a tip-splitting event has occurred and the two daughter buds have just begun to diverge towards the lateral sources of FGF10 expression. The expression of mSpry2 continues within the daughter bud epithelial tips, but at a lower level. It should be noted that the expression ofmSpry2 is extinguished between the two daughter bud tips, implying that FGF10 signaling is no longer inducing mSpry2 at the latter location. This pattern of bud extension and gene expression is then repeated as the bud tips migrate towards the band of Fgf10 expression located along the edge of the primitive lobe, which we have termed herein the APR or apical pulmonary ridge.