Fig. 8.
Directional migration of mammary epithelium requires Fgfr2 function. (A-H) Timecourse of mammary epithelial migration in response to beads soaked in FGF10. Mammary epithelium of either control (Fgfr2+/+, n=6, A-D) or mutant (Fgfr2Δ/Δ, n=5, E-H) genotype was juxtaposed with FGF10 beads at a distance of ∼100 µm. Note that although Fgfr2Δ/Δ MEC aggregates did not migrate toward FGF10-soaked beads they did grow somewhat in size during culture, as did Fgfr2+/+ MEC aggregates, presumably due to cell proliferation. Scale bars: 100 µm. (I) Model of mammary gland regeneration from basal cell transplantation, which involves at least four stages. (1) FGFR2-dependent luminal cell differentiation from basal cells. (2) Expansion of mammary epithelium composed of both basal and luminal cells. (3) Epithelial budding and ductal elongation. FGF10-FGFR2 function via both MEK and PI3K signaling is essential for collective epithelial migration and branch initiation. By contrast, ductal elongation is primarily driven by FGF2 function in an FGFR2-independent manner. (4) Repeated branching morphogenesis until the mammary fat pad is filled and a functional mammary gland is generated. (1′) In the absence of FGFR2 function, at least two of the above four steps fail to occur: Fgfr2 null basal cells fail to differentiate into luminal cells and, consequently, a functional gland fails to regenerate; (3′) when Fgfr2Δ/Δ basal and luminal cells are transplanted, epithelial migration does not occur, leading to failure in epithelial invasion, budding and thus branch initiation. As a result, a functional gland fails to regenerate.