FGF10 is an inducer and Pax6 a competence factor for lacrimal gland development

We investigated the mechanism of tissue induction and specification using t he lacrimal gland as a model system. This structure begins its morphogenesi s as a bud-like outgrowth of the conjunctival epithelium and ultimately for ms a branched structure with secretory function. Using a reporter transgene as a specific marker for gland epithelium, we show that the transcription factor Pax6 is required for normal development of the gland and is probably an important competence factor. In investigating the cell-cell signaling r equired, we show that fibroblast growth factor (FGF) 10 is sufficient to st imulate ectopic lacrimal bud formation in ocular explants, Expression of FG F10 in the mesenchyme adjacent to the presumptive lacrimal bud and absence of lacrimal gland development in FGF10-null mice strongly suggest that it i s an endogenous inducer. This was supported by the observation that inhibit ion of signaling by a receptor for FGF10 (receptor 2 IIIb) suppressed devel opment of the endogenous lacrimal bud, In explants of mesenchyme-free gland epithelium, FGF10 stimulated growth but not branching morphogenesis. This suggested that its role in induction is to stimulate proliferation and, in turn, that FGF10 combines with other factors to provide the instructive sig nals required for lacrimal gland development.