The Drosophila spitz gene encodes a putative EGF-like growth factor involved in dorsal-ventral axis formation and neurogenesis (original) (raw)
Related papers
Developmental control by the Drosophila EGF receptor homolog DER
Trends in Genetics, 1991
The DER protein has the canonical structure of a receptor tyrosine kinase belonging to the subclass that includes the vertebrate EGF receptor 1,2. While three members of this class have been identified in vertebrates, in Drosophila DER appears to be unique. The protein has a single transmembrane domain separating the intracellular and extracellular domains. The highest degree of sequence conservation is found in the intracellular kinase domain. The DER protein has also been shown to have tyrosine kinase activity, and can phosphorylate itself3. The carboxy-terminal region, beyond the kinase domain, contains the sites for autophosphorylation and shows the lowest degree of structural conservation, although this region plays a pivotal role in signal transduction (see below). The extracellular portion comprises four subdomains. Two are cysteinerich and are likely to generate the scaffold of the ligand-binding domain, but not its recognition specificity. The cysteine-rich subdomain closer to the membrane is the longer of the two. Interestingly, this structural feature is also found in the Caenorhabditis elegans EGF receptor homolog, encoded by the let-23 gene ~, but not in the vertebrate counterparts, indicating that the ancestral form of these receptors was probably similar to DER.
Development (Cambridge, England), 2002
Transforming growth factor beta signaling mediated by Decapentaplegic and Screw is known to be involved in defining the border of the ventral neurogenic region in the fruitfly. A second phase of Decapentaplegic signaling occurs in a broad dorsal ectodermal region. Here, we show that the dorsolateral peripheral nervous system forms within the region where this second phase of signaling occurs. Decapentaplegic activity is required for development of many of the dorsal and lateral peripheral nervous system neurons. Double mutant analysis of the Decapentaplegic signaling mediator Schnurri and the inhibitor Brinker indicates that formation of these neurons requires Decapentaplegic signaling, and their absence in the mutant is mediated by a counteracting repression by Brinker. Interestingly, the ventral peripheral neurons that form outside the Decapentaplegic signaling domain depend on Brinker to develop. The role of Decapentaplegic signaling on dorsal and lateral peripheral neurons is st...
Cell, 1989
Recessive lethal mutations in the genetic locus of the Drosophila EGF receptor homolog (DER) were isolated. Identification of mutations in the gene is based on assays of DER protein autophosphorylation activity. Most DER alleles show little or no in vivo autophosphorylation. The ability to monitor these activities in vivo and in vitro offers a preliminary insight into the functional defects in the different mutant proteins. The identification of the DER locus was also confirmed by partial rescue of the mutant phenotype with a DER P-element construct. Homozygous DER mutants display a complex embryonic phenotype. Most notably, the anterior structures deteriorate, ventral denticle bands are missing, the germ band does not retract, and the central nervous system shows a collapse of commissure and midline pattern. Mutations in DER were shown to be allelic to the previously described locus faint little ball.
Dissecting the roles of the Drosophila EGF receptor in eye development and MAP kinase activation
Development, 1998
A new conditional Egfr allele was used to dissect the roles of the receptor in eye development and to test two published models. EGFR function is necessary for morphogenetic furrow initiation, is not required for establishment of the founder R8 cell in each ommatidium, but is necessary to maintain its differentiated state. EGFR is required subsequently for recruitment of all other neuronal cells. The initial EGFR-dependent MAP kinase activation occurs in the furrow, but the active kinase (dp-ERK) is observed only in the cytoplasm for over 2 hours. Similarly, SEVENLESS-dependent activation results in cytoplasmic appearance of dp-ERK for 6 hours. These results suggest an additional regulated step in this pathway and we discuss models for this.
Mechanisms of Development, 1998
Activation of the Drosophila EGF-receptor (DER) is spatially and temporally controlled by the release of its various ligands. DER and its ligand Spitz mediate the formation of specific somatic muscle precursors. We show that a second DER ligand, Vein, complements the activity of Spitz in the development of various somatic muscle precursors. In vn mutant embryos, the DER-dependent muscle precursors do not form in some of the segments. This phenotype is significantly enhanced in embryos carrying only one copy of wild type spitz. Our analysis suggests that Vein activation of DER differs qualitatively from that of Spitz in that it does not lead to the expression of the inhibitory protein Argos, possibly leading to a continuous activation of the DER signaling pathway.
Developmental Biology, 2000
The Drosophila rhomboid (rho) gene participates in localized activation of EGF-receptor signaling in various developmental settings. The Rhomboid protein has been proposed to promote presentation and/or processing of the membrane-bound Spitz (mSpi) EGF-related ligand to generate an active diffusible form of the ligand. Here, we report on a new rhomboid-related gene identified by sequence similarity searching that we have named brother of rhomboid (brho). In contrast to rho, which is expressed in complex patterns during many stages of development, brho appears to be expressed only during oogenesis. brho transcripts are present in early oocytes and abut posterior follicle cells which exhibit high levels of MAPK activation. brho, like rho, collaborates with Star to promote signaling through the EGF-R/MAPK pathway, and genetic evidence indicates that Brho can activate both the mSpi and the Grk precursor EGF ligands in the wing. We propose that endogenous brho may activate the oocyte-specific Gurken ligand and thereby participate in defining posterior cell fates in the early follicular epithelium.
Development, 1998
The Drosophila ventral nerve cord derives from a stereotype population of about 30 neural stem cells, the neuroblasts, per hemineuromere. Previous experiments provided indications for inductive signals at ventral sites of the neuroectoderm that confer neuroblast identities. Using cell lineage analysis, molecular markers and cell transplantation, we show here that EGF receptor signalling plays an instructive role in CNS patterning and exerts differential effects on dorsoventral subpopulations of neuroblasts. The Drosophila EGF receptor (DER) is capable of cell autonomously specifiying medial and intermediate neuroblast cell fates. DER signalling appears to be most critical for proper development of intermediate neuroblasts and less important for medial neuroblasts. It is not required for lateral neuroblast lineages or for cells to adopt CNS midline cell fate. Thus, dorsoventral patterning of the CNS involves both DER-dependent and -independent regulatory pathways. Furthermore, we discuss the possibility that different phases of DER activation exist during neuroectodermal patterning with an early phase independent of midline-derived signals.