RT Journal Article
SR Electronic
T1 A Role of <em>ath5</em> in Inducing <em>neuroD</em> and the Photoreceptor Pathway
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7150
OP 7158
DO 10.1523/JNEUROSCI.2266-04.2004
VO 24
IS 32
A1 Wenxin Ma
A1 Run-Tao Yan
A1 Wenlian Xie
A1 Shu-Zhen Wang
YR 2004
UL http://www.jneurosci.org/content/24/32/7150.abstract
AB Photoreceptors in the vertebrate retina are light-sensitive neurons, and their degeneration results in irreversible visual loss. Understanding how photoreceptor fate is determined is a prerequisite for developing photoreceptor replacement therapies. Previous studies identified two basic helix-loop-helix genes, neurogenin2 (ngn2) and neuroD, participating in a genetic pathway leading to photoreceptor genesis. Here we present experimental data suggesting that ath5, which is known for its critical role in retinal ganglion cell development, may also lead to photoreceptor production. In the developing retina, ath5 expression was detected in two zones of cells, and coexpression with neuroD was observed in the zone adjacent to young photoreceptor cells accumulating on the retinal pigment epithelial side. Retroviral-driven misexpression of ath5 in retinal cells increased the population of photoreceptor cells, as well as ganglion cells, in a developmental stage-dependent manner that is consistent with ath5 being involved in the development of multiple types of retinal neurons. Ectopic ath5 expression in cultures of non-neural retinal pigment epithelial cells elicited transdifferentiation into cells that expressed photoreceptor-specific genes and displayed photoreceptor-like morphologies. Gene expression analysis showed that ngn2 did not induce ath5, and ath5 did not induce ngn2, but both induced neuroD and RaxL. These data suggest a pathway of “ath5 → neuroD → photoreceptor genes” separate from yet convergent with the ngn2 pathway.