A global survey identifies novel upstream components of the Ath5 neurogenic network


Investigating the architecture of gene regulatory networks (GRNs) is essential to decipher the logic of developmental programs during embryogenesis. In this study we present an upstream survey approach, termed trans-regulation screen, to comprehensively identify the regulatory input converging on endogenous regulatory sequences. Our dual luciferase-based screen queries transcriptome-scale collections of cDNAs. Using this approach we study the regulation of Ath5, the central node in the GRN controlling retinal ganglion cell (RGC) specification in vertebrates. The Ath5 promoter integrates the input of upstream regulators to enable the transient activation of the gene, which is an essential step for RGC differentiation. We efficiently identified potential Ath5 regulators that were further filtered for true positives by an in situ hybridization screen. Their regulatory activity was validated in vivo by functional assays in medakafish embryos. Our analysis establishes functional groups of genes controlling different regulatory phases, including the onset of Ath5 expression at cell-cycle exit and its down-regulation prior to terminal RGC differentiation. These results extent the current model of the GRN controlling retinal neurogenesis in vertebrates.

DOI: 10.1186/gb-2009-10-9-r92

Extracted Key Phrases

1 Figure or Table

Citations per Year

160 Citations

Semantic Scholar estimates that this publication has 160 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Souren2009AGS, title={A global survey identifies novel upstream components of the Ath5 neurogenic network}, author={Marcel Souren and Juan R Mart{\'i}nez-Morales and Panagiota Makri and Beate Wittbrodt and Joachim Wittbrodt}, journal={Genome Biology}, year={2009}, volume={10}, pages={R92 - R92} }