Foxc2^CreERT2 knock-in mice mark stage-specific Foxc2-expressing cells during mouse organogenesis

Foxc2, a member of the winged helix transcription factor family, is essential for eye, calvarial bone, cardiovascular and kidney development in mice. Nevertheless, how Foxc2-expressing cells and their descendent cells contribute to the development of these tissues and organs has not been elucidated. Here, we generated a Foxc2 knock-in (Foxc2^CreERT2) mouse, in which administration of estrogen receptor antagonist tamoxifen induces nuclear translocation of Cre recombinase in Foxc2-expressing cells. By crossing with ROSA-LacZ reporter mice (Foxc2^CreERT2; R26R), the fate of Foxc2 positive (Foxc2⁺) cells was analyzed through LacZ staining at various embryonic stages. We found Foxc2⁺cell descendants in the supraoccipital and exoccipital bone in E18.5 embryos, when tamoxifen was administered at embryonic day (E) 8.5. Furthermore, Foxc2⁺ descendant cranial neural crest cells at E8–10 were restricted to the corneal mesenchyme, while Foxc2⁺ cell derived cardiac neural crest cells at E6–12 were found in the aorta, pulmonary trunk and valves, and endocardial cushions. Foxc2⁺ cell descendant contributions to the glomerular podocytes in the kidney were also observed following E6.5 tamoxifen treatment. Our results are consistent with previous reports of Foxc2 expression during early embryogenesis and the Foxc2^CreERT2 mouse provides a tool to investigate spatiotemporal roles of Foxc2 and contributions of Foxc2⁺ expressing cells during mouse embryogenesis.