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Publication : Transformation of cone precursors to functional rod photoreceptors by bZIP transcription factor NRL.

First Author  Oh EC Year  2007
Journal  Proc Natl Acad Sci U S A Volume  104
Issue  5 Pages  1679-84
PubMed ID  17242361 Mgi Jnum  J:119504
Mgi Id  MGI:3702354 Doi  10.1073/pnas.0605934104
Citation  Oh EC, et al. (2007) Transformation of cone precursors to functional rod photoreceptors by bZIP transcription factor NRL. Proc Natl Acad Sci U S A 104(5):1679-84
abstractText  Networks of transcriptional regulatory proteins dictate specification of neural lineages from multipotent retinal progenitors. Rod photoreceptor differentiation requires the basic motif-leucine zipper (bZIP) transcription factor NRL, because loss of Nrl in mice (Nrl-/-) results in complete transformation of rods to functional cones. To examine the role of NRL in cell fate determination, we generated transgenic mice that express Nrl under the control of Crx promoter in postmitotic photoreceptor precursors of WT and Nrl-/- retina. We show that NRL expression, in both genetic backgrounds, leads to a functional retina with only rod photoreceptors. The absence of cones does not alter retinal lamination, although cone synaptic circuitry is now recruited by rods. Ectopic expression of NRL in developing cones can also induce rod-like characteristics and partially suppress cone-specific gene expression. We show that NRL is associated with specific promoter sequences in Thrb (encoding TRbeta2 transcription factor required for M-cone differentiation) and S-opsin and may, therefore, directly participate in transcriptional suppression of cone development. Our studies establish that NRL is not only essential but is sufficient for rod differentiation and that postmitotic photoreceptor precursors are competent to make binary decisions during early retinogenesis.
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