Abstract

To better understand the mechanisms that govern the development of retinal neurons, it is critical to gain additional insight into the specific intrinsic factors that control cell fate decisions and neuronal maturation. In the developing mouse retina, Atoh7, a highly conserved transcription factor, is essential for retinal ganglion cell development. Moreover, Atoh7 expression in the developing retina occurs during a critical time period when progenitor cells are in the process of making cell fate decisions. We performed transcriptome profiling of Atoh7+ individual cells isolated from mouse retina. One of the genes that we found significantly correlated with Atoh7 in our transcriptomic data was the E3 ubiquitin ligase, Trim9. The correlation between Trim9 and Atoh7 coupled with the expression of Trim9 in the early mouse retina led us to hypothesize that this gene may play a role in the process of cell fate determination. To address the role of Trim9 in retinal development, we performed a functional analysis of Trim9 in the mouse and did not detect any morphological changes in the retina in the absence of Trim9. Thus, Trim9 alone does not appear to be involved in cell fate determination or early ganglion cell development in the mouse retina. We further hypothesize that the reason for this lack of phenotype may be compensation by one of the many additional TRIM family members we find expressed in the developing retina.

Highlights

  • The retina is a powerful tool for studying the central nervous system and has been intensively investigated for over a century[1]

  • To gain insight into the mechanisms of cell fate determination operating within the retina, single cells were isolated from mouse retinas at various developmental timepoints and microarray hybridization was performed[10]

  • We found many members of the Tripartite motif (Trim) family widely expressed in retinal progenitor cells (RPCs) transcriptomes (Fig 1A)

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Summary

Introduction

The retina is a powerful tool for studying the central nervous system and has been intensively investigated for over a century[1]. It is organized as a laminar tissue, comprised of six different neuronal cell types and one glial cell type. These functionally and morphologically diverse groups of cells arise from a pool of multipotent retinal progenitor cells (RPCs)[2,3,4,5]. Neurogenesis begins at about embryonic day (E)11.5.

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