Krüppel-Like Factor 4 (KLF4) Is Not Required for Retinal Cell Differentiation.

Jiahua Fang,Jeffrey L Goldberg,Yan Wang,Peter X Shaw

doi:10.1523/eneuro.0117-15.2016

Abstract

During early vertebrate eye development, a regulatory network of transcription factors regulates retinal cell differentiation and survival into adulthood. Among those factors, Krüppel-like factor 4 (KLF4) plays the dual role of maintaining the stem cell status of retinal progenitors cells and repressing the intrinsic axon regeneration ability in retinal ganglion cells (RGCs) after injury. This study further investigated whether KLF4 plays a role in early retinal cell differentiation or survival into adulthood. We examined different types of retinal neurons, including RGCs, amacrine cells, bipolar cells, Müller cells, and photoreceptor cells, in adult mice in which KLF4 was conditionally deleted in early retinal development using Chx10-promoted Cre by immunohistochemistry. We compared the numbers of retinal neurons and the thickness of photoreceptor and nerve fiber layers between Chx10–Cre-driven KLF4 deletion mice and wild-type mice. There was no significant difference in cell number among any of the retinal cell types or in photoreceptor layer thickness with KLF4 deletion during early development. The thickness of axon bundles in the nerve fiber layer in the Chx10 conditional KLF4 knock-out mice was greater than that in wild-type mice. These results suggest that KLF4 is not required for retinal cell differentiation or survival, but does normally limit retinal ganglion cell axon bundle thickness. These data support a hypothesis that KLF4 suppresses axon growth during development.

Highlights

The neural retina comprises six types of neurons and one type of glial cell (Müller cell)
To investigate whether the development of photoreceptors is influenced by retinal expression of Krüppel-like factor 4 (KLF4), we examined recoverin on retinal cross sections of conditional knock-out (KLF4-cKO) and WT control mice
We found no significant difference in the thickness of recoverinϩ retinal immunostaining in WT versus KLF4-cKO mice (p Ͼ 0.1; Fig. 2C)

Summary

Introduction

The neural retina comprises six types of neurons (retinal ganglion cells, amacrine, horizontal, bipolar, and rod and cone photoreceptors) and one type of glial cell (Müller cell). They are generated from a common pool of multi-. In the early stages of retinal development, RPCs generate these different cell types under the regulation of a combination of extrinsic and intrinsic influences (Livesey and Cepko, 2001). The ability of RPCs to generate particular progeny is specified by transcription factors that define their competence to differentiate into single or perhaps subsets of retinal cell types (Cepko, 1999). Transcription factors known to regulate these functions include members of the basic helix-loop-helix (Hatakeyama and Kageyama, 2004; Yao et al, 2010), homeodomain (Dorval et al, 2005), and forkhead families (Moose et al, 2009)

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Conclusion