Figure 4

Brn4 expression is reduced in the POM of TCre-KO embryos, and Brn4^-; Tbx1^+/- embryo display defects in cochlea coiling. Sagittal sections of control (A) and TCre-KO (B) embryos at E10.5 stained with an Ab against Brn4. Expression in the POM is lost in TCre-KO embryos, however neural tube (nt) expression is unaffected. Brn4^-;Tbx1^+/- embryos display a shortened cochlear duct. Lateral views of paint-filled membranous labyrinths at E15.5–E16.0 of Tbx1^+/- (E), Brn4^+/-;Tbx1^+/- (F), Brn4^-(G, H), Brn4^-;Tbx1^+/- (I, J). The fully developed mouse cochlea normally completes 1.75 turns, and all inner ears of Tbx1^+/- mutants and Brn4^+/-;Tbx1^+/- exhibited normal cochlear growth (E, F). The majority of Brn4^- mutant inner ears also displayed a normal cochlea (G), while 20% displayed a slightly shortened cochlea (H). All inner ears Brn4^-;Tbx1^+/- mutants exhibited a malformed cochlea that failed to form a second turn and instead displayed abnormal twisting or bifurcation (I, J). Arrows point to the cochlear duct in H-J. The endolymphatic sac in E, F, G and J was present but did not fill with paint. cvg, cochleovestibular ganglion; ov, otic vesicle; nt, neural tube; pom, periotic mesenchyme. Scale bar in D is 200 μm, scale bar in F is 350 μm.