Fig. 8. Possible signaling crosstalks in the whole distal GT region including the DUE. (A) SEM picture of an embryonic genital tubercle (GT) at 12.5 dpc. The yellow region shows the location of the DUE. (B) Coronal sections of the boxed region in A. DUE, which expresses Fgf8, locates adjacent to the outer-most epithelial layer (yellow region) aligned with normal GT ectoderm (region between black broken lines). (C) Possible crosstalks in the distal GT mesenchymes including BMP4, WNT5A may underlie the alteration of cell survival or of cell proliferation. Previous studies suggested Fgf8 as a growth stimulatory factor (Haraguchi et al., 2000). This study indicated a possibility that it could also work as a survival factor. (D) Ablation of BMP signaling in the Bmpr1a mutant distal GT region is shown, which may be modulated by distal GT epithelia (double-headed arrows; possibly also by distal-dorsal epithelia) and GT mesenchyme. Epithelial derived (either from the outer-most epithelial layer or from the adjacent GT ectoderm) signals may affect Fgf8 expression in the DUE and consequently affect apoptosis. Putative positive signaling factors are indicated by blue characters and negative signaling factors are indicated by red characters. The antagonist, noggin, is shown in green.