Direct and indirect effects of hedgehog pathway activation in the mammalian retina

The morphogen Sonic hedgehog (Shh) is expressed by the projection neurons of the retina, retinal ganglion cells (RGCs) and promotes retinal precursor cell (RPC) proliferation. To distinguish between direct and indirect effects of Hedgehog (Hh) pathway activation in the perinatal mouse retina, we followed the fate of cells that expressed a constitutively active allele of Smoothened (SMO-M2), the signal transduction component of the Hh pathway. SMO-M2 expression promoted a cell-autonomous increase in CyclinD1 expression and RPC proliferation and promoted the development of cells with an inner nuclear layer identity. SMO-M2 expression also inhibited rhodopsin expression in uninfected cells, thus highlighting an unexpected non-cell autonomous effect of Hh pathway activation on photoreceptor development.