NeuroD1 is required for survival of photoreceptors but not pinealocytes: Results from targeted gene deletion studies
Article first published online: 16 AUG 2012
Published 2012. This article is a US Government work and is in the public domain in the USA
Journal of Neurochemistry
Volume 123, Issue 1, pages 44–59, October 2012
How to Cite
Ochocinska, M. J., Muñoz, E. M., Veleri, S., Weller, J. L., Coon, S. L., Pozdeyev, N., Michael Iuvone, P., Goebbels, S., Furukawa, T. and Klein, D. C. (2012), NeuroD1 is required for survival of photoreceptors but not pinealocytes: Results from targeted gene deletion studies. Journal of Neurochemistry, 123: 44–59. doi: 10.1111/j.1471-4159.2012.07870.x
- Issue published online: 10 SEP 2012
- Article first published online: 16 AUG 2012
- Accepted manuscript online: 11 JUL 2012 09:00PM EST
- Received April 25, 2012; revised manuscript received June 20, 2012; accepted July 6, 2012.
- gene expression;
- pineal gland;
- transcriptome profiling
NeuroD1 encodes a basic helix-loop-helix transcription factor involved in the development of neural and endocrine structures, including the retina and pineal gland. To determine the effect of NeuroD1 knockout in these tissues, a Cre/loxP recombination strategy was used to target a NeuroD1 floxed gene and generate NeuroD1 conditional knockout (cKO) mice. Tissue specificity was conferred using Cre recombinase expressed under the control of the promoter of Crx, which is selectively expressed in the pineal gland and retina. At 2 months of age, NeuroD1 cKO retinas have a dramatic reduction in rod- and cone-driven electroretinograms and contain shortened and disorganized outer segments; by 4 months, NeuroD1 cKO retinas are devoid of photoreceptors. In contrast, the NeuroD1 cKO pineal gland appears histologically normal. Microarray analysis of 2-month-old NeuroD1 cKO retina and pineal gland identified a subset of genes that were affected 2–100-fold; in addition, a small group of genes exhibit altered differential night/day expression. Included in the down-regulated genes are Aipl1, which is necessary to prevent retinal degeneration, and Ankrd33, whose protein product is selectively expressed in the outer segments. These findings suggest that NeuroD1 may act through Aipl1 and other genes to maintain photoreceptor homeostasis.