<Emphasis Type="Italic">Drosophila</Emphasis><Emphasis Type="Italic">P</Emphasis> transposons of the urochordata <Emphasis Type="Italic">Ciona intestinalis</Emphasis>

P transposons belong to the eukaryotic DNA transposons, which are transposed by a cut and paste mechanism using a P-element-coded transposase. They have been detected in Drosophila, and reside as single copies and stable homologous sequences in many vertebrate species. We present the P elements Pcin1, Pcin2 and Pcin3 from Ciona intestinalis, a species of the most primitive chordates, and compare them with those from Ciona savignyi. They showed typical DNA transposon structures, namely terminal inverted repeats and target site duplications. The coding region of Pcin1 consisted of 13 small exons that could be translated into a P-transposon-homologous protein. C. intestinalis and C. savignyi displayed nearly the same phenotype. However, their P elements were highly divergent and the assumed P transposase from C. intestinalis was more closely related to the transposase from Drosophila melanogaster than to the transposase of C. savignyi. The present study showed that P elements with typical features of transposable DNA elements may be found already at the base of the chordate lineage. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Expression of the human FUSED protein in <Emphasis Type="Italic">Drosophila</Emphasis>

The Drosophila segment polarity gene fused, which encodes a serine threonine kinase, is required to transmit the Hedgehog (Hh) signal in imaginal discs. To explore the functional homology between the human protein FUSED (hFU) and the Drosophila protein fused (dFu), we have subjected hFU to a precise and well-defined Hh signalling assay of Drosophila wing development. In the wildtype, hFU affects the expression of Hh target genes leading thus to defects in adult wings. In fu mutants, overexpression of hFU cannot rescue the fu phenotype. These results suggest that hFU in Drosophila interferes with endogenous Hh signalling probably by competing with endogenous dFu when binding its partners but cannot perform the normal Fu function.Edited by C. Desplan     

Genetic regions that interact with loss- and gain-of-function phenotypes of <Emphasis Type="Italic">deltex</Emphasis> implicate novel genes in <Emphasis Type="Italic">Drosophila</Emphasis> Notch signaling

The Notch signaling pathway is an evolutionarily conserved mechanism that regulates many cell fate decisions. The deltex (dx) gene encodes an E3-ubiquitin ligase that binds to the intracellular domain of the Notch protein and regulates Notch signaling in a positive manner. However, it is still not clear how Dx does this. We generated a transgenic line, GMR-dx, which overexpresses dx in the developing Drosophila eye disc. The GMR-dx line showed a rough-eye phenotype, specific transformation of a photoreceptor cell (R3 to R4), and a rotation defect in the ommatidia. This phenotype was suppressed in combination with a dx loss-of-function mutant, indicating that it was due to a dx gain-of-function. We previously reported that overexpression of Dx results in the stabilization of Notch in late endosomes. Here, we found that three motifs in Dx, a region that binds to Notch, a proline-rich motif and a RING-H2 finger, were required for this stabilization, although the relative activity of these variants in this assay did not always correspond to the severity of the rough-eye phenotype. In an attempt to identify novel genes of the Notch pathway, we tested a large collection of chromosomal deficiencies for the ability to modify the eye phenotypes of the GMR-dx line. Twelve genomic segments that enhanced the rough-eye phenotype of GMR-dx were identified. To evaluate the specificity of these interactions, we then determined whether the deletions also interacted with the wing phenotypes associated with a loss-of-function mutation of dx, dx²⁴. Analyses based on whole-genome information allowed us to conclude that we have identified two novel loci that probably include uncharacterized genes involved in Dx-mediated Notch signaling.     

Evolutionary History and Mode of the <Emphasis Type="Italic">amylase</Emphasis> Multigene Family in <Emphasis Type="Italic">Drosophila</Emphasis>

Previous studies indicate that the tandemly repeated members of the amylase (Amy) gene family evolved in a concerted manner in the melanogaster subgroup and in some other species. In this paper, we analyzed all of the 49 active and complete Amy gene sequences in Drosophila, mostly from subgenus Sophophora. Phylogenetic analysis indicated that the two types of diverged Amy genes in the Drosophila montium subgroup and Drosophila ananassae, which are located in distant chromosomal regions from each other, originated independently in different evolutionary lineages of the melanogaster group after the split of the obscura and melanogaster groups. One of the two clusters was lost after duplication in the melanogaster subgroup. Given the time, 24.9 mya, of divergence between the obscura and the melanogaster groups (Russo et al. 1995), the two duplication events were estimated to occur at about 13.96 ± 1.93 and 12.38 ± 1.76 mya in the montium subgroup and D. ananassae, respectively. An accelerated rate of amino acid changes was not observed in either lineage after these gene duplications. However, the G+C contents at the third codon positions (GC3) decreased significantly along one of the two Amy clusters both in the montium subgroup and in D. ananassae right after gene duplication. Furthermore, one of the two types of the Amy genes with a lower GC3 content has lost a specific regulatory element within the montium subgroup species and D. ananassae. While the tandemly repeated members evolved in a concerted manner, the two types of diverged Amy genes in Drosophila experienced frequent gene duplication, gene loss, and divergent evolution following the model of a birth-and-death process.     

Selective Pressures on <Emphasis Type="Italic">Drosophila</Emphasis> Chemosensory Receptor Genes

The evolution and patterns of selection of genes encoding 10 Drosophila odorant receptors (Or) and the sex pheromone receptor Gr68a were investigated by comparing orthologous sequences across five to eight ecologically diverse species of Drosophila. Using maximum likelihood estimates of dN/dS ratios we show that all 11 genes sampled are under purifying selection, indicating functional constraint. Four of these genes (Or33c, Or42a, Or85e, and Gr68a) may be under positive selection, and if so, there is good evidence that 12 specific amino acid sites may be under positive selection. All of these sites are predicted to be located either in loop regions or just inside membrane spanning regions, and interestingly one of the two sites in Gr68a is in a similar position to a previously described polymorphism in Gr5a that causes a shift in sensitivity to its ligand trehalose. For three Ors, possible evidence for positive selection was detected along a lineage. These include Or22a in the lineage leading to D. mauritiana and Or22b in the lineage leading to D. simulans. This is of interest in light of previous data showing a change in ligand response profile for these species in the sensory neuron (ab3A) which expresses both Or22a and Or22b in D. melanogaster. In summary, while the main chemosensory function and/or structural integrity of these 10 Or genes and Gr68a are evolutionarily preserved, positive selection appears to be acting on some of these genes, at specific sites and along certain lineages, and provides testable hypotheses for further functional experimentation. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. [Reviewing Editor: Dr. David Pollock]     

Functional conservation of the human <Emphasis Type="Italic">EXT1</Emphasis> tumor suppressor gene and its <Emphasis Type="Italic">Drosophila</Emphasis> homolog <Emphasis Type="Italic">tout</Emphasis><Emphasis Type="Italic">velu</Emphasis>

Heparan sulfate proteoglycans play a vital role in signaling of various growth factors in both Drosophila and vertebrates. In Drosophila, mutations in the tout velu (ttv) gene, a homolog of the mammalian EXT1 tumor suppressor gene, leads to abrogation of glycosaminoglycan (GAG) biosynthesis. This impairs distribution and signaling activities of various morphogens such as Hedgehog (Hh), Wingless (Wg), and Decapentaplegic (Dpp). Mutations in members of the exostosin (EXT) gene family lead to hereditary multiple exostosis in humans leading to bone outgrowths and tumors. In this study, we provide genetic and biochemical evidence that the human EXT1 (hEXT1) gene is conserved through species and can functionally complement the ttv mutation in Drosophila. The hEXT1 gene was able to rescue a ttv null mutant to adulthood and restore GAG biosynthesis.     

Molecular genetics of the<Emphasis Type="Italic"> Alhambra</Emphasis> (<Emphasis Type="Italic"> Drosophila AF10</Emphasis>) complex locus of<Emphasis Type="Italic"> Drosophila</Emphasis>

The Alhambra ( Alh) gene is the Drosophila homologue of the human AF10 gene. AF10 has been identified as a fusion partner of MLL, a human homologue of the fly gene trithorax, in infant leukemias. The endogenous function of human AF10 is not known, but may be vital to its role in acute leukemia. This prompted us to analyse Alh function. We describe here the genetic organisation of the Alh locus in D. melanogaster. We show that an independent lethal complementation group encoding a muscle protein ( Mlp84B) is located within an Alh intron. We have already shown that the leucine zipper (LZ) domain of ALH activates several Polycomb group-responsive elements. We further demonstrate that the LZ domain on its own bears the Alh vital function, since it is necessary and sufficient for rescue of Alh mutant lethality. Finally, we demonstrate that, in contrast to a previous report, Alh does not affect position-effect variegation.Communicated by G. Reuter     

Use of gain-of-function study to delineate the roles of<Emphasis Type="Italic">crumbs</Emphasis> in<Emphasis Type="Italic">Drosophila</Emphasis> eye development

The cell polarity gene,crumbs (crb), has been shown to participate in the development and degeneration of theDrosophila retina. Mutations inCRB1, the human homologue ofDrosophila crb, also result in retinitis pigmentosa and Leber congential amaurosis. In this study, we used the gain-of-function approach to delineate the roles ofcrb in developingDrosophila eye. In the third-instar larval stage, eye development is initiated with photoreceptor differentiation and positioning of photoreceptor nuclei in the apical cellular compartment of retinal epithelium. In the pupal stage, differentiated photoreceptors begin to form the photosensitive structures, the rhabdomeres, at their apical surface. UsingGMR-Gal4 to drive overexpression of the Crb protein at the third-instar eye disc, we found that differentiation of photoreceptors was disrupted and the nuclei of differentiated photoreceptors failed to occupy the apical compartment. Usinghs-Gal4 to drive Crb overexpression in pupal eyes resulted in interference with extension of the adherens junctions and construction of the rhabdomeres, and these defects were stage-dependent. This gain-of-function study has enabled us to delineate the roles of Crb at selective stages of eye development inDrosophila.     

<Emphasis Type="Italic">Drosophila</Emphasis> retinophilin contains MORN repeats and is conserved in humans

The function of conserved novel human genes can be efficiently addressed in genetic model organisms. From a collection of genes expressed in the Drosophila visual system, cDNAs expressed in vertebrates were identified and one similar to a novel human gene was chosen for further investigation. The results reported here characterize the Drosophila retinophilin gene and demonstrate that a similar gene is expressed in the human retina. The Drosophila and human retinophilin sequences are 50% identical, and they share an additional 16% conserved substitutions. Examination of the cDNA and genomic sequence indicates that it corresponds to the gene CG10233 of the annotated genome and predicts a 22.7 kDa protein. Polyclonal antibodies generated to a predicted retinophilin peptide recognize an antigen in Drosophila photoreceptor cells. The retinophilins encode 4 copies of a repeat associated with a Membrane Occupation and Recognition Nexus (MORN) function first discovered in junctophilins, which may interact with the plasma membrane. These results therefore show that Drosophila retinophilin is expressed in fly photoreceptor cells, demonstrate that a conserved human gene is expressed in human retina, and suggest that a mutational analysis of the Drosophila gene would be valuable.     

Evolution of the<Emphasis Type="Italic"> Drosophila broad</Emphasis> locus: the<Emphasis Type="Italic"> Manduca sexta broad</Emphasis> Z4 isoform has biological activity in<Emphasis Type="Italic"> Drosophila</Emphasis>

The Drosophila melanogaster broad locus is essential for normal metamorphic development. Broad encodes three genetically distinct functions (rbp, br, and 2Bc) and a family of four zinc-finger DNA-binding proteins (Z1-Z4). The Z1, Z2, and Z3 protein isoforms are primarily associated with the rbp, br, and 2Bc genetic functions respectively. The Z4 protein isoform also provides some rbp genetic function, however an essential function for the Z4 isoform in metamorphosis has not been identified. To determine the degree of conservation of Z4 function between the tobacco hornworm Manduca sexta and Drosophila we generated transgenic Drosophila expressing the Manduca broad Z4 isoform and used this transgene to rescue rbp mutant lethality during Drosophila metamorphosis. We find that the Manduca Z4 protein has significant biological activity in Drosophila with respect to rescue of rbp-associated lethality. There was also some overlap in effects on cuticle gene expression between the Manduca Z4 and Drosophila Z1 isoforms that was not shared with the Drosophila Z4 isoform. Our findings show that Z4 function has been conserved over the 260-million-year period since the divergence of Diptera and Lepidoptera, and are consistent with the hypothesis that the Drosophila Z4 and Manduca Z4 isoforms have essential roles in metamorphosis.Edited by M. Akam     

Functional constraint and divergence in the G protein family in <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis> and <Emphasis Type="Italic">Caenorhabditis briggsae</Emphasis>

Part of the challenge of the post-genomic world is to identify functional elements within the wide array of information generated by genome sequencing. Although cross-species comparisons and investigation of rates of sequence divergence are an efficient approach, the relationship between sequence divergence and functional conservation is not clear. Here, we use a comparative approach to examine questions of evolutionary rates and conserved function within the guanine nucleotide-binding protein (G protein) gene family in nematodes of the genus Caenorhabditis. In particular, we show that, in cases where the Caenorhabditis elegans ortholog shows a loss-of-function phenotype, G protein genes of C. elegans and Caenorhabditis briggsae diverge on average three times more slowly than G protein genes that do not exhibit any phenotype when mutated in C. elegans, suggesting that genes with loss of function phenotypes are subject to stronger selective constraints in relation to their function in both species. Our results also indicate that selection is as strong on G proteins involved in environmental perception as it is on those controlling other important processes. Finally, using phylogenetic footprinting, we identify a conserved non-coding motif present in multiple copies in the genomes of four species of Caenorhabditis. The presence of this motif in the same intron in the gpa-1 genes of C. elegans, C. briggsae and Caenorhabditis remanei suggests that it plays a role in the regulation of gpa-1, as well as other loci.Electronic Supplementary Material Supplementary material is available for this article at     

<Emphasis Type="Italic">SQUA</Emphasis>-like genes in the orchid <Emphasis Type="Italic">Phalaenopsis</Emphasis> are expressed in both vegetative and reproductive tissues

The SQUA family (AP1/FUL family) of MADS-box genes plays an important role in the transition from the vegetative to the reproductive development of angiosperms, and its origin might be concurrent with fixation of floral structure in angiosperms. Here, we isolated two Phalaenopsis MADS-box genes designated ORAP11 and ORAP13, both of which belong to the monocot FUL-like clade of the SQUA family. RT-PCR showed that both genes are strongly expressed in the floral bud, and also detected in the vegetative organs. During later stages, ORAP11 was only detected in the column, but ORAP13 signal was absent from all of the floral organs. In-situ hybridization experiments detected both genes in the tips and margins of developing petals and lips, the developing column, and ovule. Over-expression of both genes in tobacco induced early flowering and changed plant architecture. Our results suggest that in Phalaenopsis, both genes might share partly redundant activities and play important roles in the process of floral transition and morphological architecture. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

<Emphasis Type="Italic">Anthocyaninless1</Emphasis> gene of <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis> encodes a UDP-glucose:flavonoid-3-<Emphasis Type="Italic">O</Emphasis>-glucosyltransferase

We isolated several mutants of Arabidopsis thaliana (L.) Heynh. that accumulated less anthocyanin in the plant tissues, but had seeds with a brown color similar to the wild-type. These mutants were allelic with the anthocyaninless1 (anl1) mutant that has been mapped at 15.0 cM of chromosome 5. We performed fine mapping of the anl1 locus and determined that ANL1 is located between the nga106 marker and a marker corresponding to the MKP11 clone. About 70 genes are located between these two markers, including three UDP-glucose:flavonoid-3-O-glucosyltransferase-like genes and a glutathione transferase gene (TT19). A mutant of one of the glucosyltransferase genes (At5g17050) was unable to complement the anl1 phenotype, showing that the ANL1 gene encodes UDP-glucose:flavonoid-3-O-glucosyltransferase. ANL1 was expressed in all tissues examined, including rosette leaves, stems, flower buds and roots. ANL1 was not regulated by TTG1.     

Mutational analysis of the <Emphasis Type="Italic">gum</Emphasis> gene cluster required for xanthan biosynthesis in <Emphasis Type="Italic">Xanthomonas</Emphasis><Emphasis Type="Italic">oryzae</Emphasis> pv <Emphasis Type="Italic">oryzae</Emphasis>

Genome sequence analysis of Xanthomonas oryzae pv. oryzae has revealed a cluster of 12 ORFs that are closely related to the gum gene cluster of Xanthomonas campestris pv. campestris. The gum gene cluster of X. oryzae encodes proteins involved in xanthan production; however, there is little experimental evidence supporting this. In this study, biochemical analyses of xanthan produced by a defined set of X. oryzae gum mutant strains allowed us to preliminarily assign functions to most of the gum gene products: biosynthesis of the pentasaccharide repeating unit for GumD, GumM, GumH, GumK, and GumI, xanthan polymerization and transport for GumB, GumC, GumE, and GumJ, and modification of the pentasaccharide repeating unit for GumF, GumG, and GumL. In addition, we found that the exopolysaccharides are essential but not specific for the virulence of X. oryzae. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Sang-Yoon Kim and Jeong-Gu Kim contributed equally to this work.     

Characterization of <Emphasis Type="Italic">twist</Emphasis> and <Emphasis Type="Italic">snail</Emphasis> gene expression during mesoderm and nervous system development in the polychaete annelid <Emphasis Type="Italic">Capitella</Emphasis> sp. I

To investigate the evolutionary history of mesoderm in the bilaterian lineage, we are studying mesoderm development in the polychaete annelid, Capitella sp. I, a representative lophotrochozoan. In this study, we focus on the Twist and Snail families as candidate mesodermal patterning genes and report the isolation and in situ expression patterns of two twist homologs (CapI-twt1 and CapI-twt2) and two snail homologs (CapI-sna1 and CapI-sna2) in Capitella sp. I. CapI-twt1 is expressed in a subset of mesoderm derivatives during larval development, while CapI-twt2 shows more general mesoderm expression at the same stages. Neither twist gene is detected before the completion of gastrulation. The two snail genes have very distinct expression patterns. At cleavage and early gastrula stages, CapI-sna1 is broadly expressed in precursors of all three germ layers and becomes restricted to cells around the closing blastopore during late gastrulation; CapI-sna2 expression is not detected at these stages. After gastrulation, both snail genes are expressed in the developing central nervous system (CNS) at stages when neural precursor cells are internalized, and CapI-sna1 is also expressed laterally within the segmental mesoderm. Based on the expression patterns in this study, we suggest a putative function for Capitella sp. I twist genes in mesoderm differentiation and for snail genes in regulating CNS development and general cell migration during gastrulation. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

<Emphasis Type="Italic">Rab11</Emphasis> is required for myoblast fusion in <Emphasis Type="Italic">Drosophila</Emphasis>

Rab11, an evolutionarily conserved, ubiquitously expressed subfamily of small monomeric Rab GTPases, has been implicated in regulating vesicular trafficking through the recycling of endosomal compartment. In order to gain an insight into the role of this gene in myogenesis during embryonic development, we have studied the expression pattern of Rab11 in mesoderm during muscle differentiation in Drosophila embryo. When dominant-negative or constitutively active Drosophila Rab11 proteins are expressed or Rab11 is reduced via double-stranded RNA in muscle precursors, they cause partial failure of myoblast fusion and show anomalies in the shape of the muscle fibres. Our results suggest that Rab11 plays no role in cell fate specification in muscle precursors but is required late in the process of myoblast fusion. This work was supported by grants from the DST (to J.K.R.) and SRF from ICMR, New Delhi (to T.B.).     

Expression of <Emphasis Type="Italic">defective proventriculus</Emphasis> during head capsule development is conserved in <Emphasis Type="Italic">Drosophila</Emphasis> and stalk-eyed flies (<Emphasis Type="Italic">Diopsidae</Emphasis>)

Hypercephaly, in the form of lateral extensions of the head capsule, is observed in several families of Diptera. A particularly exaggerated form is found in Diopsid stalk-eyed flies, in which both eyes and antennae are laterally displaced at the end of stalks. The processes of early development and specification of the head capsule in stalk-eyed flies are similar to those in Drosophila melanogaster. In Drosophila the homeobox gene ocelliless (oc) shows a mediolateral gradient of expression across the region of the eye-antennal imaginal disc that gives rise to the head capsule and specifies the development of different head structures. The genes and developmental mechanisms that subsequently define head shape in Drosophila and produce hypercephaly in stalk-eyed flies remain unclear. To address this, we performed an enhancer trap screen for Drosophila genes expressed in the same region as oc and identified the homeobox gene defective proventriculus (dve). In the eye-antennal imaginal disc, dve is coexpressed with oc in the region that gives rise to the head capsule and is active along the medial edge of the antennal disc and in the first antennal segment. Analyses of dve expression in mutant eye-antennal discs are consistent with it acting downstream of oc in the development of the head capsule. We confirm that orthologues of dve are present in a diverse panel of five stalk-eyed fly species and analyse patterns of dve sequence variation within the clade. Our results indicate that dve expression and sequence are both highly conserved in stalk-eyed flies.M. Carr and I. Hurley contributed equally to this work.     

The costae presenting in high-temperature-induced <Emphasis Type="Italic">vestigial</Emphasis> wings of <Emphasis Type="Italic">Drosophila</Emphasis>: implications for anterior wing margin formation

It has long been noted that high temperature produces great variation in wing forms of the vestigial mutant of Drosophila. Most of the wings have defects in the wing blade and partially formed wing margin, which are the result of autonomous cell death in the presumptive wing blade or costal region of the wing disc. The vestigial gene (vg) and the interaction of Vg protein with other gene products are well understood. With this biochemical knowledge, reinvestigations of the high-temperature-induced vestigial wings and the elucidation of the molecular mechanism underlying the large-scale variation of the wing forms may provide insight into further understanding of development of the wing of Drosophila. As a first step of such explorations, I examined high-temperature-induced (29°C) vestigial wings. In the first part of this paper, I provide evidences to show that the proximal and distal costae in these wings exhibit regular and continuous variation, which suggests different developmental processes for the proximal and distal costal sections. Judging by the costae presenting in the anterior wing margin, I propose that the proximal and distal costal sections are independent growth units. The genes that regulate formation of the distal costal section also strongly affect proliferation of cells nearby; however, the same phenomenon has not been found in the proximal costal section. The distal costal section seems to be an extension of the radius vein. vestigial, one of the most intensely researched temperature-sensitive mutations, is a good candidate for the study of marginal vein formation. In the second part of the paper, I regroup the wing forms of these wings, chiefly by comparison of venation among these wings, and try to elucidate the variation of the wing forms according to the results of previous work and the conclusions reached in the first part of this paper, and provide clues for further researches.     

Morphological characterization of single fan-shaped body neurons in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

The fan-shaped body is the largest substructure of the central complex in Drosophila melanogaster. Two groups of large-field neurons that innervate the fan-shaped body, viz., F1 and F5 neurons, have recently been found to be involved in visual pattern memory for “contour orientation” and “elevation” in a rut-dependent manner. The F5 neurons have been found to be responsible for the parameter “elevation” in a for-dependent manner. We have shown here that the F1 neuron also affects visual memory for “contour orientation” in a for-dependent way. With the help of Gal4/UAS and FLP-out techniques, we have characterized the morphological features of these two groups of neurons at single neuron resolution. We have observed that F1 or F5 neurons are groups of isomorphic individual neurons. Single F1 neurons have three main arborization regions: one in the first layer of the fan-shaped body, one in the ventral body, and another in the inferior medial protocerebrum. Single F5 neurons have two arborization regions: one in the fifth layer of the fan-shaped body and the other in the superior medial protocerebrum. The polarity of the F1 and F5 neurons has been studied with the Syt-GFP marker. Our results indicate the existence of presynaptic sites of both F1 and F5 neurons located in the fan-shaped body and postsynaptic sites outside of the fan-shaped body. This work was supported by the “973 Program” (2005CB522804 and 2009CB918702), the National Natural Sciences Foundation of China (30621004, 30625022, and 30770682), and the Knowledge Innovation Program of the Chinese Academy of Sciences (KSCX2-YW-R-28).     

In vivo evidence for a regulatory role of the kinase activity of the <Emphasis Type="Italic">linotte</Emphasis>/<Emphasis Type="Italic">derailed</Emphasis> receptor tyrosine kinase,a <Emphasis Type="Italic">Drosophila</Emphasis> Ryk ortholog

The RYK subfamily of receptor tyrosine kinases is characterised by unusual, but highly conserved, amino acid substitutions in the kinase domain. The linotte/derailed gene encodes a Drosophila RYK subfamily member involved in embryonic and adult central nervous system development. Previous studies have shown that the kinase activity of this receptor is not required in vivo for its embryonic function. In this study, we have investigated the role of the cytoplasmic domain and the kinase activity of the linotte/derailed receptor tyrosine kinase in adult brain development. Our results indicate that these domains are not essential for adult brain development but they are required for the proper regulation of the activity of this receptor. This sheds light on a regulatory role for the kinase activity of a RYK subfamily member.Edited by C DesplanEmmanuel Taillebourg and Caroline Moreau-Fauvarque contributed equally to this work