Fig. 8. Blocking Tgfß signaling rescues bud formation and gene
expression in the lung field of RA-deficient foregut. (A-D)
BMS493-treated mouse foregut fails to induce lung bud formation (A, asterisks;
E, asterisk, boxed region). However, treatment with a combination of BMS493
and pan-specific TGFß-blocking antibody (TAb) allows bud formation and
strong Nkx2.1 signals are detected in the prospective lung region of
the WT foregut (B, arrowheads). (C,D) Similarly, untreated
Raldh2-/- foregut does not form lung buds under the
control condition (C, asterisk), but budding and Nkx2.1 expression
are partially rescued by TAb treatment (D, arrowheads). (E,F) In
BMS493-treated WT foregut, Fgf10 mRNA is seen in the thyroid and
pancreatic fields, but not in the prospective lung region (E, boxed area). In
WT foregut treated with both BMS493 and TAb, there is strong Fgf10
expression (F, boxed area) associated with the rescued lung bud (F,
arrowhead). Panels to the right are the corresponding enhanced-contrast images
of the explants in E and F. Th, thyroid; Ht, heart; Lu, lung; Pa, pancreas;
CAb, unrelated isotype-matched control antibody. Scale bar: 270 µm in
A.