Abstract
c-Jun N-terminal kinases (JNKs) regulate cell proliferation and differentiation via phosphorylating such transcription factors as c-Jun. The function of JNKs in retinogenesis remains to be elucidated. Here, we report that knocking out Jnk1, but not Jnk2, increased the number of photoreceptors, thus enhancing the electroretinogram (ERG) responses. Intriguingly, Notch1, a well-established negative regulator of photoreceptor genesis, was significantly attenuated in Jnk1 knockout (KO) mice compared to wild-type mice. Mechanistically, light specifically activated JNK1 to phosphorylate c-Jun, which in turn induced Notch1 transcription. The identified JNK1–c-Jun–Notch1 axis strongly inhibited photoreceptor-related transcriptional factor expression and ultimately impaired photoreceptor opsin expression. Our study uncovered an essential function of JNK1 in retinogenesis, revealing JNK1 as a potential candidate for targeting ophthalmic diseases.
Highlights
The retina is a thin sheet of neural tissue in the eye that senses light and transmits relevant information to the brain via the optic nerve
We confirmed that JNK1 and JNK2 were depleted in the Jnk1 KO mice and
Retinas from Jnk1 KO mice and Jnk2 KO mice exhibited normal cell layer lamination: the outer plexiform layer, inner plexiform layer, and ganglion cell layer (GCL) were of similar thickness to the corresponding layers of wild-type retinas and showed no obvious morphological abnormalities
Summary
The retina is a thin sheet of neural tissue in the eye that senses light and transmits relevant information to the brain via the optic nerve. The vertebrate retina consists of six types of neurons and one type of glial cells (Müller glial cells), which form three cellular layers: photoreceptors in the outer nuclear layer (ONL); horizontal, bipolar, and amacrine interneurons and Müller glial cells in the inner nuclear layer (INL); and ganglion and displaced amacrine cells in the ganglion cell layer (GCL). These cell types play specific roles in the process of vision [1,2]. Cones are early-born cells, with production peaking at E14.5 and E15.5 in the central and peripheral areas of the retina, respectively
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