Spatio-temporal regulation of Dachsous proteins expressed during Drosophila development

Abstract

Transcriptional regulation is one of the main mechanisms involved in tissue morphogenesis to give rise to functional organs with characteristic shapes. The Drosophila dachsous (ds) gene plays a key role in tissue development and tumorigenesis by controlling planar cell polarity (PCP), tissue growth, patterning and mitochondrial activity, among other processes. Disturbance of ds expression during Drosophila development results in alterations of the function and morphology of a wide range of embryonic and larval tissues. Similarly, in humans, mutations in the DCHS1 gene cause severe congenital malformations due to a global impairment affecting the normal formation of many tissues and organs. However, the transcriptional mechanism governing the expression of ds gene remains poorly understood. Here, we perform transcriptional analysis of ds expression and identify novel embryonic Ds proteins not expressed in larvae. The comparative analysis of Ds proteins and the exon expression pattern in/of two regulatory alleles such as dsD36 and ds38K further suggests the existence of specific transcriptional ds variants at different stages. Furthermore, a search for regulatory elements that control the spatial and temporal pattern of ds revealed the presence of cis-regulatory elements located in the intronic regions, which regulate the expression of these Ds proteins. Finally, using the Drosophila wing as model to perform a functional analysis, we show that wing growth and PCP are differentially regulated by Ds proteins expressed in different regions of wing disc. The present findings reveal that the complex regulation of the ds gene ensures the expression of specific Ds protein isoforms at different developmental stages in order to activate the cell-specific molecular programs required for tissue morphogenesis.