Details

Autor(en) / Beteiligte

• Ochocinska, Margaret J.
• Muñoz, Estela M.
• Veleri, Shobi
• Weller, Joan L.
• Coon, Steven L.
• Pozdeyev, Nikita
• Michael Iuvone, P.
• Goebbels, Sandra
• Furukawa, Takahisa
• Klein, David C.

Titel

NeuroD1 is required for survival of photoreceptors but not pinealocytes: Results from targeted gene deletion studies

Ist Teil von

• Journal of neurochemistry, 2012-10, Vol.123 (1), p.44-59

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. ‘New light on NeuroD1 and vision’1) This study was performed to investigate the post‐natal role of the developmental transcription factor NeuroD1 in the retina and pineal gland. 2) The most relevant novel finding in our article is the identification of retinal and pineal transcripts that are affected by the NeuroD1 deletion and that NeuroD1 is required for proper post‐natal survival and physiological function of the retinal photoreceptors. 3) This finding is important as it demonstrates the persistent role of developmental regulators throughout post‐natal life and identifies new downstream targets of NeuroD1 that are important for photoreceptor homeostasis in the vertebrate retina.