Figure 7. Bmp7 modulates positional identity through activation of the Tak1 pathway.

(a)Maximum z-projections of phalloidin-labeled BP cultures illustrating hair cell density at the proximal and distal ends of BP explants after 6 days IV under the indicated conditions (see text for details). Inhibition of Tak1 (oxozeanol) induces decreased hair cell density in the distal region of the BP, consistent with a more proximal phenotype. This phenotype contrasts with the effects of Bmp7 and is comparable to the effects of treatment with Chrdl1 (Fig. 4). In contrast, explants treated with both Bmp7 and oxozeanol appear comparable to control.(b) Quantification of mean hair cell density in BPs treated with oxozeanol alone or oxozeanol and Bmp7. Oxozeanol treatment leads to a significant decrease in distal density and elimination of the density gradient. In contrast, treatment with Oxozeanol and Bmp7 has no effect on the density gradient. (c,d). Data showquantification or hair cell lumenal surface area and bundle volume for the same conditions as in b. For both, Oxozeanol-treatment induces changes consistent with distalization of the BP while treatment with Oxozeanol and Bmp7 has no effect on tonotopic patterning. All data are presented as mean ± sem. Stars indicate a p value < 0.05, Student's t-test. Controls n = 14, oxozeanol n = 5, oxo + Bmp7 n = 8. (e)Western blot for total (upper) and phosphorylated (lower) Tak1 in E8 BPs in response to treatment with Bmp7. A rapid increase in levels of p-Tak1 is observed following Bmp7 treatment. Scale bar in a = 100 μm.