Altered expression of genes of the Bmp/Smad and Wnt/calcium signaling pathways in the cone-only Nr1-/- mouse retina, revealed by gene profiling using custom cDNA microarrays

Jindan Yu, Shirley He, James S. Friedman, Masayuki Akimoto, Debashis Ghosh, Alan J. Mears, David Hicks, Anand Swaroop*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Many mammalian retinas are rod-dominant, and hence our knowledge of cone photoreceptor biology is relatively limited. To gain insights into the molecular differences between rods and cones, we compared the gene expression profile of the rod-dominated retina of wild type mouse with that of the cone-only retina of Nr1-/- (Neural retina leucine zipper knockout) mouse. Our analysis, using custom microarrays of eye-expressed genes, provided equivalent data using either direct or reference-based experimental designs, confirmed differential expression of rod- and cone-specific genes in the Nr1-/- retina and identified novel genes that could serve as candidates for retinopathies or for functional studies. In addition, we detected altered expression of several genes that encode cell signaling or structural proteins. Prompted by these findings, additional real-time PCR analysis revealed that genes belonging to the Bmp/Smad and Wnt/Ca2+ signaling pathways are expressed in the mature wild type retina and that their expression is significantly altered in the Nr1 -/- retina. Chromatin immunoprecipitation analysis of adult retina identified Bmp4 and Smad4, which are down-regulated in the Nr1-/- retina, as possible direct transcriptional targets of Nr1. Consistent with these studies, Bmp4 and Smad4 are expressed in the mature rod photoreceptors of mouse retina. Modulation of Bmp4 and/or Smad4 by Nr1 may provide a mechanism for integrating diverse cell signaling networks in rods. We hypothesize that Bmp/Smad and Wnt/Ca2+ pathways participate in cell-cell communication in the mature retina, and expression changes observed in the Nr1-/- retina reflect their biased utilization in rod versus cone homeostasis.

Original languageEnglish (US)
Pages (from-to)42211-42220
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number40
DOIs
StatePublished - Oct 1 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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