Abstract:
Ten-Eleven Translocation Proteins (TETs) are epigenetic enzymes that regulate gene expression in metazoans, thereby influencing several of their biological processes such as stem cell differentiation and neurodevelopment. These dioxygenases activate gene expression by demethylating DNA and thus, deregulating mutations in Tet genes are associated with gliomas and neurological disorders. Drosophila melanogaster expresses a single Tet (dTet) making it a valuable model for studying the effects of Tet deregulation on central nervous system (CNS) development.
Using the UAS-Gal4 system, dTet was overexpressed in different CNS tissues and its phenotypic effects on larval ventral nerve cord (VNC) length and optic lobe area were assessed by confocal microscopy. Moreover, UAS-Gal80 was used to temporally control the overexpression of dTET in differentiated glia to determine the developmental stage at which aberrant phenotypes manifest.
The VNC was significantly elongated in the larvae overexpressing dTet in all glia, which contributed together to produce this aberrant phenotype. Elongation and widening of the VNC were also observed in the larvae overexpressing dTet in cortical glia, accompanied by an enlargement in the optic lobes. dTet overexpression in neuroblasts affected CNS morphogenesis as well, during what seems to be a sensitive time window in their differentiation to Ganglion Mother Cells (GMCs). As for perineurial glia, they seem to be the main glial subpopulation regulating the morphogenesis of the abdominal segments of the VNC. They have also been shown to play a role alongside cortical glia in the morphogenesis of the optic lobes.
The findings of this study reveal the roles of dTet in the different stages of the CNS development, which are tissue-specific and have implications in disease modeling and therapeutic applications. These findings are also foundational for studying the effects of dTet deregulation on CNS development at the molecular level.
