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Figure 9


Fig. 9. A summary of how different levels of Shh mediate the formation of inner ear structures in the wild type and various mutants. A wild-type inner ear receives graded levels of Shh protein during development, highest in the ventral region and decreasing towards the dorsal region. This graded Shh signaling results in various levels of Gli activator (blue triangle) and repressor (red triangle) activities within the otocyst that are responsible for mediating the formation of different inner ear structures. The distal region of the cochlear duct (blue) requires the activator function of Gli proteins that is redundantly shared by Gli2 and Gli3, and possibly Gli1. The proximal region of the cochlear duct and the saccule (pale red and pale blue) requires relatively low levels of Shh signaling, as compared with the distal region, to remove Gli3R. The dorsal region of the inner ear (red) requires a correct dose of Gli3R balanced by the least amount of Shh signaling. In the various mutants, the missing inner ear structures are outlined in grey. The absence of GliA (blue) affected the distal region of the cochlear duct in all mutants analyzed. For most mutants, the formation of the saccule and the proximal region of the cochlear duct are affected in those situations in which Gli3R is not properly alleviated by Shh signaling (dark red rectangle, Shh-/-; pink rectangle, Shh-/-;Gli3+/-). In addition, the semicircular canal region is also partially affected in the absence of Gli3R (white, Gli3-/- and Shh-/-;Gli3-/-) or in the presence of too much Gli3R (dark red, Shh-/-). The exception is the normalcy of the vestibule and proximal cochlear duct region in the Gli3{Delta}699 mutant, in which Gli3R levels cannot be alleviated. We attributed the absence of vestibular and proximal cochlear defects in this mutant to the presumably normal function of Gli1/Gli2A. There is a temporal difference in the requirement of Gli3R and Shh for lateral canal formation (asterisks).





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