Two transcription factors can direct three photoreceptor outcomes from rod precursor cells in mouse retinal development

L Ng, A Lu, A Swaroop, DS Sharlin… - Journal of …, 2011 - Soc Neuroscience
L Ng, A Lu, A Swaroop, DS Sharlin, A Swaroop, D Forrest
Journal of Neuroscience, 2011Soc Neuroscience
The typical mammalian visual system is based upon three photoreceptor types: rods for dim
light vision and two types of cones (M and S) for color vision in daylight. However, the
process that generates photoreceptor diversity and the cell type in which diversity arises
remain unclear. Mice deleted for thyroid hormone receptor β2 (TRβ2) and neural retina
leucine zipper factor (NRL) lack M cones and rods, respectively, but gain S cones. We
therefore tested the hypothesis that NRL and TRβ2 direct a common precursor to a rod, M …
The typical mammalian visual system is based upon three photoreceptor types: rods for dim light vision and two types of cones (M and S) for color vision in daylight. However, the process that generates photoreceptor diversity and the cell type in which diversity arises remain unclear. Mice deleted for thyroid hormone receptor β2 (TRβ2) and neural retina leucine zipper factor (NRL) lack M cones and rods, respectively, but gain S cones. We therefore tested the hypothesis that NRL and TRβ2 direct a common precursor to a rod, M cone, or S cone outcome using Nrlb2/b2 “knock-in” mice that express TRβ2 instead of NRL from the endogenous Nrl gene. Nrlb2/b2 mice lacked rods and produced excess M cones in contrast to the excess S cones in Nrl−/− mice. Notably, the presence of both factors yielded rods in Nrl+/b2 mice. The results demonstrate innate plasticity in postmitotic rod precursors that allows these cells to form three functional photoreceptor types in response to NRL or TRβ2. We also detected precursor cells in normal embryonic retina that transiently coexpressed Nrl and TRβ2, suggesting that some precursors may originate in a plastic state. The plasticity of the precursors revealed in Nrlb2/b2 mice suggests that a two-step transcriptional switch can direct three photoreceptor fates: first, rod versus cone identity dictated by NRL, and second, if NRL fails to act, M versus S cone identity dictated by TRβ2.
Soc Neuroscience