Investigate the Role of Deltex Genes in Neural Development and Brain Tumorigenesis

The signaling pathways regulating neural development usually also play a role in brain tumorigenesis, and understanding of these signaling pathways may lead to novel therapies and strategies that will advance the treatment of brain tumors. The aim of this study is to identify a novel regulatory mechanism in both neural development and brain tumorigenesis, and we will focus on Deltex/DELTEX proteins. Deltex proteins are potential mediators for Notch signaling and are implicated in neural development, however, the function of these proteins is mostly unknown. Our previous studies revealed different degrees of alternation of DELTEX1, DELTEX3, and DELTEX4 expression in several brain tumor samples; and we found that Deltex1 and Deltex4 are capable of regulating the proliferation, differentiation, and apoptosis of neural progenitors in zebrafish embryos. Accordingly, we will evaluate the role of these deltex/DELTEX genes and the underlying mechanism in brain tumor cell lines and in the developing nervous system of zebrafish. In addition, tumor cells with altered DELTEX expression will be transplanted into the brains of zebrafish to fully characterize the dynamic and spatial characteristics of tumor cells in a transparent in vivo vertebrate system. Since how the Deltex-dependent transduction is achieved is poorly understood, we will also analyze the role of Deltex proteins in Notch signaling and perform genome-wide microarray analysis to identify their downstream targets in developing neural tissues and brain tumors. This will be the first study to address the potential oncogenic/tumor-suppressive character of DELTEXs in different types of brain tumor cells and its role in the brain tumorigenic niche. This work will be collaborated with attending physicians, Dr Tu-Hsueh Yeh (Department of Neurology) and Dr Yin-Cheng Huang (Department of Neurosurgeon) in Chang Gung Memorial Hospital.

Project ID:PA10301-0155
External Project ID:NSC102-2311-B182-002-MY3