Em. Levine et al., SONIC HEDGEHOG PROMOTES ROD PHOTORECEPTOR DIFFERENTIATION IN MAMMALIAN RETINAL CELLS IN-VITRO, The Journal of neuroscience, 17(16), 1997, pp. 6277-6288
The hedgehog gene family encodes secreted proteins important in many d
evelopmental patterning events in both vertebrates and invertebrates.
In the Drosophila eye disk, hedgehog controls the progression of photo
receptor differentiation in the morphogenetic furrow. To investigate w
hether hedgehog proteins are also involved in the development of the v
ertebrate retina at stages of photoreceptor differentiation, we analyz
ed expression of the three known vertebrate hedgehog genes. We found t
hat Sonic hedgehog and Desert hedgehog are expressed in the developing
retina, albeit at very low levels, whereas Indian hedgehog (lhh) is e
xpressed in the developing and mature retinal pigmented epithelium, be
ginning at embryonic day 13. To determine whether hedgehog proteins ha
ve activities on developing retinal cells, we used an in vitro system
in which much of retinal histogenesis N-terminal recombinant Sonic Hed
gehog protein (SHH-N) was added to rat retinal cultures for 3-12 d, an
d tile numbers of retinal cells of various phenotypes were analyzed by
immunohistochemistry. We found that SHH-N caused a transient in creas
e in the number of retinal progenitor cells, and a 2- to 10-fold incre
ase in the number of photoreceptors differentiating in the cultures wh
en analyzed with three different photoreceptor-specific antigens, In c
ontrast, the numbers of retinal ganglion cells and amacrine cells were
similar to those in control cultures. These results show that Hedgeho
g proteins can regulate mitogenesis and photoreceptor differentiation
in the vertebrate retina, and Ihh is a candidate factor from the pigme
nted epithelium to promote retinal progenitor proliferation and photor
eceptor differentiation.