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Branching morphogenesis is a molecularly conserved mechanism that is adopted by several organs, such as the lung, kidney, mammary gland and salivary gland, to maximize the surface area of a tissue within a small volume. Branching occurs through repetitive clefting and elongation of spherical epithelial structures, called endbuds, which invade the surrounding mesenchyme. In the salivary gland, lumen formation takes place alongside branching morphogenesis, but in a controlled manner, so that branching is active at the distal ends of epithelial branches while lumen formation initiates at the proximal ends, and spreads distally. We present here data showing that interaction between FGF signaling and the canonical (β-catenin dependent) and non-canonical branches of Wnt signaling coordinates these two processes. Using the Axin2(lacZ) reporter mice, we find Wnt/β-catenin signaling activity first in the mesenchyme and later, at the time of lumen formation, in the ductal epithelium. Gain and loss of function experiments reveal that this pathway exerts an inhibitory effect on salivary gland branching morphogenesis. We have found that endbuds remain devoid of Wnt/β-catenin signaling activity, a hallmark of ductal structures, through FGF-mediated inhibition of this pathway. Our data also show that FGF signaling has a major role in the control of lumen formation by preventing premature hollowing of epithelial endbuds and slowing down the canalization of presumptive ducts. Concomitantly, FGF signaling strongly represses the ductal marker Cp2l1, most likely via repression of Wnt5b and non-canonical Wnt signaling. Inhibition of canonical and non-canonical Wnt signaling in endbuds by FGF signaling occurs at least in part through sFRP1, a secreted inhibitor of Wnt signaling and downstream target of FGF signaling. Altogether, these findings point to a key function of FGF signaling in the maintenance of an undifferentiated state in endbud cells by inhibition of a ductal fate., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Salivary glands are a group of organs secreting a watery substance that is of utmost importance for several physiological functions ranging from the protection of teeth and surrounding soft tissues to the lubrication of the oral cavity, which is crucial for speech and perception of food taste. Salivary glands are complex networks of hollow tubes and secretory units that are found in specific locations of the mouth and which, although architecturally similar, exhibit individual specificities according to their location. This chapter focuses on the embryonic development of vertebrate salivary glands, which has been classically studied in the mouse model system since the 1950s. We describe here where, when and how major salivary glands develop in the lower jaw of the mouse embryo. Key mechanisms involved in this process are discussed, including reciprocal tissue interactions between epithelial and mesenchymal cells, epithelial branching morphogenesis and coordinated cell death and cell proliferation., (Copyright 2010 S. Karger AG, Basel.)