Identification of Novel Factors Involved in the Development of the Nervous System

Neural development begins by the formation of neural ectoderm. Four genes, HESX1, OTX2, GBX2, and SIX3, play key roles in this formation. The neural development process continues by the differentiation of neural ectoderm to the neural plate, leading to the development of neural tube and neural crest cells, which give rise to the central and peripheral nervous system, respectively. These processes are mainly regulated by a cascade of developmental transcription factors. Phylogenetic profiling is a method that detects the evolutionarily patterns of genes. The main premise of this method is that the genes that have evolved together are likely to share common functional or structural features. In this work, I hypothesize that the four neural ectoderm genes (HESX1, OTX2, GBX2, and SIX3) are evolutionarily correlated with each other, and have similar or correlated evolutionary patterns to that of the genes involved in neural development. In this work, I first determined the correlation amongst the phylogenetic profiles of the four neural ectoderm factors and identified, in a genome-wide study, the genes that are highly correlated with these factors in order. The study led to identification of 35 genes that are correlated to four neural ectoderm factors, suggesting novel interactions or molecular players in the development of the nervous system. We then examined the spatial and temporal expression patterns of the neural ectoderm factors and their putative interacting partners in the developing mouse brain, using Allen Brain Atlas. Our result show that from these 35 genes, POU4F1, PAX7, DMBX1, PITX2, OTP, PHOX2B and ARX have the most similar expression patterns to those of the four neural ectoderm genes. These
results suggest novel players in the pathways that are responsible for the development of the three primary vesicles of the brain. The results also might lead to the discovery of non-canonical functions for the four neural ectoderm genes.