Zinc Finger Protein Broad Regulates Neuroepithelial Cell Transformation In The Drosophila Optic Lobe

Broad protein is a member of the BTB transcription factor family,including four protein subtypes: Br-Z1,Br-Z2,Br-Z3 and Br-Z4.Broad protein is induced early in response to ecdysone signaling,thereby promoting metamorphosis.In the Drosophila optic lobe,Broad is dynamically expressed,starting at late-second larval instar,reaching a peak level at late-third larval instar.Studies have found that either inactivation or overexpression of Broad protein affects the normal development of the Drosophila optic lobe.Overexpression of Broad protein promotes the transformation of the optic lobe neuroepithelial cells into neural stem cells,whereas inactivation of Broad protein inhibits the transformation of neuroepithelial cells into neural stem cells.However,it is not known how Broad converts the optic lobe neuroepithelial cells into neural stem cells.In this study,we aimed to undertand the mechanism by which Broad protein transforms neuroepithelial cells into neural stem cells.We first re-examined the phenotypes of Broad inactivation or overexpression in the optic lobe.We then performed transcriptome analyses to identify Broad target genes in the Drosophila brain.Our data indicates that loss of Broad protein led to down regulation of 944 genes but also up-regulation of 1065 genes.We next selected 21 down-regulated genes and 16 up-regulated genes for verification by quantitative real-time PCR(q RT-PCR)analyses.The success rate of q PCR was 97%,validating the transcriptome data.We find that in br RNAi brains,29 genes of the protease complex pathway are down reglated,so are 26 genes of the protein-processing pathway in the endoplamic reticulum;on the other hand,there are 16 genes of the glysolysis/gluconeogenesis pathways,14 genes of neuroactive ligand-receptor pathways and 9 genes in the beta-alanine metabolism pathway that are up-regulated.Therefore,we speculate that Broad inactivation inhibits the transformation of neuroepithelial cells into neural stem cells by down-regulating genes of proteasomes and protein processing in endoplasmic reticulum or up-regulating genes involved in glycolysis/gluconeogenesis,neuroactive ligand-receptor pathways and beta-alanine metabolism.