The Trim family of genes and the retina: Expression and functional characterization.

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.

ALS-associated genes display CNS expression in the developing zebrafish.

Amyotrophic lateral sclerosis (ALS) is characterized by progressive muscle atrophy resulting from the deterioration of motor neurons in the central nervous system (CNS). Recent genome-wide association studies have revealed several genes linked to ALS, further demonstrating the complexity of the disease. The zebrafish (Danio rerio) is an attractive model organism to study the function of the rapidly expanding number of ALS-associated genes, in part, due to the development of genome editing techniques that have facilitated specific gene targeting. Before investing in the manipulation and phenotypic examination of these genes, however, it is important to ascertain the localization of expression in this organism. We performed an expression analysis of 29 total ALS-linked genes in the developing zebrafish, specifically focusing on those genes that displayed robust and reproducible expression at multiple different timepoints. First, we classified a subset of the most robustly expressed genes into three distinct groups: head-only expression, head and weak trunk expression, and head and robust trunk expression. Then, we defined the characteristic pattern of each gene at 2, 3, and 4 days post fertilization. This analysis will facilitate improved mutant phenotype assessment in zebrafish by focusing researchers on the areas of expression.