The SR Family Proteins B52 and dASF/SF2 Modulate Development of the Drosophila Visual System by Regulating Specific RNA Targets

Abstract

Deciphering the role of alternative splicing in developmental processes relies on the identification of key genes whose expression is controlled by splicing regulators throughout the growth of a whole organism. Modulating the expression levels of five SR proteins in the developing eye of Drosophila melanogaster revealed that these splicing factors induce various phenotypic alterations in eye organogenesis and also affect viability. Although the SR proteins dASF/SF2 and B52 caused defects in ommatidia structure, only B52 impaired normal axonal projections of photoreceptors and neurogenesis in visual ganglia. Microarray analyses revealed that many transcripts involved in brain organogenesis have altered splicing profiles upon both loss and gain of B52 function. Conversely, a large proportion of transcripts regulated by dASF/SF2 are involved in eye development. These differential and specific effects of SR proteins indicate that they function to confer accuracy to developmental gene expression programs by facilitating the cell lineage decisions that underline the generation of tissue identities.

SUPPLEMENTAL MATERIAL

We are indebted to the personnel of the Montpellier Rio Imaging (MRI) facility for excellent technical assistance in direct and confocal microscopy experiments. Thanks are also due to D. Severac and the personnel of the Montpellier transcriptome platform for help in microarray analyses, to J. Lis for providing us with the BBS transgenic line, to S. Sakr for skillful assistance in RT-PCR analyses, and to Y. Barash for motif predictions and statistical analyses. We are grateful to G. Cavalli for helpful discussions and to B. Blencowe for critical reading of the manuscript.

M. Gabut is a recipient of a fellowship from the Association pour la Recherche contre le Cancer (ARC). This work was supported by grants from the Agence Nationale de la Recherche (ANR-05-BLAN-0261-01) and European Alternative Splicing Network of Excellence (EURASNET, FP6 Life Sciences, Genomics and Biotechnology for Health).