Accumulating evidence suggests that Sonic hedgehog (Shh) signaling plays a crucial
role in eye vesicle patterning in vertebrates. Shh promotes expression of Pax2 in
the optic stalk and represses expression of Pax6 in the optic cup. Shh signaling contributes
to establishment of both proximal-distal and dorsal-ventral axes by activating Vax1,
Vax2, and Pax2. In the dorsal part of the developing retina, Bmp4 is expressed and
antagonizes the ventralizing effects of Shh signaling through the activation of Tbx5
expression in chick and Xenopus. To examine the roles of Shh signaling in optic cup
formation and optic stalk development, we utilized the Smoothened (Smo) conditional
knockout (CKO) mouse line. Smo is a membrane protein which mediates Shh signaling
into inside of cells. Cre expression was driven by Fgf15 enhancer. The ventral evagination
of the optic cup deteriorated from E10 in the Smo-CKO, whereas the dorsal optic cup
and optic stalk develop normally until E11. We analyzed expression of various genes
such as Pax family (Pax2/Pax6), Vax family (Vax1/Vax2) and Bmp4. Bmp4 expression was
greatly upregulated in the optic vesicle by the 21-somite stage. Then Vax1/2 expression
was decreased at the 20- to 24-somite stages. Pax2/6 expression was affected at the
27- to 32-somite stages. Our data suggest that the effects of the absence of Shh signaling
on Vax1/Vax2 are mediated through increased Bmp4 expression throughout the optic cup.
Also unchanged patterns of Raldh2 and Raldh3 suggest that retinoic acid is not the
downstream to Shh signaling to control the ventral optic cup morphology.
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