Abstract
Proper retinal cell differentiation is essential for establishing a functional retina. The purpose of this study is to investigate the role of early growth response 1 (egr1), a transcription factor (TF) that has been reported to control eye development and function, on retinal differentiation in zebrafish. Specifically, cellular changes in the Egr1-knockdown retinas were characterized by immunohistochemistry at 72 and 120 hours post-fertilization (hpf). The results indicate that Egr1 knockdown specifically suppressed the differentiation of subtypes of amacrine cells (ACs) and horizontal cells (HCs), including Parvalbumin- and GABA-positive ACs as well as Islet1-positive HCs. In addition, the knockdown induced a general delay of development of the other retinal cell types. These differentiation problems, particularly the ones with the ACs and HCs, also compromised the integrity of the inner and outer plexiform layers. In the Egr1-knockdown retinas, the expression of ptf1a, a TF that controls the specification of ACs and HCs, was prolonged and found in ectopic locations in the retina up to 72 hpf. Then, it became restricted to the proliferative marginal zone as in the control retinas at 120 hpf. This abnormal and prolonged expression of ptf1a during retinogenesis might affect the differentiation of ACs and HCs in the Egr1-knockdown retinas.
Highlights
The vertebrate retina is consisted of six types of neurons and one major type of glial cell [1]
Different cell types in the inner nuclear layer (INL) and outer nuclear layer (ONL) differentiated better and became comparable to the controls, except for Parvalbumin+ and GABA+ amacrine cells (ACs), as well as Islet1+ horizontal cells (HCs). These findings indicate that there was a specific defect in the differentiation of AC and HC subtypes in the Egr1-knockdown retinas; while for the other retinal cell types, the knockdown caused a delay in their differentiation
The signal was detected in the ganglion cell layer (GCL) in addition to the AC region at 52 hpf (Figure 1B), a stage when the retinal lamination is first established
Summary
The vertebrate retina is consisted of six types of neurons and one major type of glial cell [1]. These cells are organized into a laminated structure characterized by three distinctive cellular layers including the ganglion cell layer (GCL), inner nuclear layer (INL) and outer nuclear layer (ONL). These cellular layers are separated by two synaptic layers including the inner plexiform layer (IPL) and outer plexiform layer (OPL). The cell body of Muller cells (MCs), the major glial cell type, is located in the middle part of INL. The ONL is composed of the cell bodies of both rod and cone photoreceptors (PRs)
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