Drosophila Dyrk2 Plays a Role in the Development of the Visual System

Nathan Luebbering,Vaughn Cleghon,Mark Charlton-Perkins,Justin P Kumar,Stephanie M Rollmann,Tiffany Cook,Mark A Frye

doi:10.1371/journal.pone.0076775

Abstract

The DYRKs (dual-specificity tyrosine phosphorylation-regulated kinases) are a conserved family of protein kinases that are associated with a number of neurological disorders, but whose biological targets are poorly understood. Drosophila encodes three Dyrks: minibrain/Dyrk1A, DmDyrk2, and DmDyrk3. Here we describe the creation and characterization of a DmDyrk2 null allele, DmDyrk21w17. We provide evidence that the smell impaired allele smi35A1, is likely to encode DmDyrk2. We also demonstrate that DmDyrk2 is expressed late in the developing third antennal segment, an anatomical structure associated with smell. In addition, we find that DmDyrk2 is expressed in the morphogenetic furrow of the developing eye, that loss of DmDyrk2 in the eye produced a subtle but measurable defect, and that ectopic DmDyrk2 expression in the eye produced a strong rough eye phenotype characterized by increased secondary, tertiary and bristle interommatidial cells. This phenotype was dependent on DmDyrk2 kinase activity and was only manifest when expressed in post-mitotic non-neuronal progenitors. Together, these data indicate that DmDyrk2 is expressed in developing sensory systems, that it is required for the development of the visual system, and that the eye is a good model to identify DmDyrk2 targets.

Highlights

DYRKs are a newly emerging family of protein kinases first recognized as a distinct group in 1996 [1]
To generate a DmDyrk2 null allele, we re-mobilized l(2)k11509, and used PCR analysis to screen for imprecise excision events that deleted the P-element and neighboring genomic sequences
The DmDyrk2 locus spans nearly 50 kb, with l(2)k11509 located within its first intron, 540 bp downstream of a single predicted transcriptional start site (TSS) [20,21] and,36 kb upstream of its coding sequence (CDS)

Summary

Introduction

DYRKs are a newly emerging family of protein kinases first recognized as a distinct group in 1996 [1]. The Dyrks are an evolutionarily ancient family with members present in all eukaryotic supergroups for which genome sequences are available [4]. The Dyrk family, part of the CMGC (cyclin-dependent kinase, mitogen activated protein kinase, glycogen synthase kinase, CDC-like kinase) group of protein kinases, can be subdivided into five categories or subfamilies, Class 1, Class 2, Yaks, HIPKs, and Prp4s [4,5]. Class 1 and 2 Dyrks represent the original, best-characterized DYRK family members, and will hereafter be referred to as the Dyrks. Drosophila encodes a single Class 1 member, minibrain (Mnb)/Dyrk1A, and two Class 2 family members, smi35A/DmDyrk and DmDyrk3 [6]

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Results

Conclusion