(Downloading may take up to 30 seconds.
If the slide opens in your browser, select File -> Save As to save it.)
Click on image to view larger version.

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
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).