What's new in edition 40 part 1/5 August 2004 Gene sites new with this edition

A search engine for the SDB website, including the Interactive Fly, is now available through the Society for Developmental Biology.

The Interactive Fly was first released July/August 1996, with updates provided at approximately one month intervals, through September 1997 (edition 13). Updating quarterly started with edition 14. With this edition, the Interactive Fly has scheduled updates three times a year: fall, winter and spring.

The 'What's New' sections are more accurately termed, 'Some of What's New'. Every new gene site is included, but only about 10% of the information added to previously included gene sites is listed in the What's New sections for any given edition.

Your comments and corrections are most welcome, and needed. Please keep them coming to brodyt@codon.nih.gov

Gene sites new with this edition of the Interactive Fly:

Armitage

Polarization of the microtubule cytoskeleton during early oogenesis is required to specify the posterior of the Drosophila oocyte: this is essential for asymmetric mRNA localization during mid-oogenesis and for embryonic axis specification. The posterior determinant oskar mRNA is translationally silent until mid-oogenesis. Mutations in armitage (armi) and in three components of the RNAi pathway disrupt oskar mRNA translational silencing, polarization of the microtubule cytoskeleton, and posterior localization of oskar mRNA. armitage encodes a homolog of SDE3, a presumptive RNA helicase involved in posttranscriptional gene silencing (RNAi) in Arabidopsis, and is required for RNAi in Drosophila ovaries. Armitage forms an asymmetric network associated with the polarized microtubule cytoskeleton and is concentrated with translationally silent oskar mRNA in the oocyte. It is concluded that RNA silencing is essential for establishment of the cytoskeletal polarity that initiates embryonic axis specification and for translational control of oskar mRNA (Cook, 2004). As a RNA helicase involved in posttranscriptional gene silencing, armi mutant male germ cells fail to silence Stellate, a gene regulated endogenously by RNAi, and lysates from armi mutant ovaries are defective for RNAi in vitro. Native gel analysis of protein-siRNA complexes in wild-type and armi mutant ovary lysates suggests that armi mutants support early steps in the RNAi pathway but are defective in the production of active RNA-induced silencing complex (RISC), which mediates target RNA destruction in RNAi. These results suggest that armi is required for RISC maturation (Tomari, 2004).

Blistery

Tensin is an actin-binding protein that is localized in focal adhesions. At focal adhesion sites, tensin participates in the protein complex that establishes transmembrane linkage between the extracellular matrix and cytoskeletal actin filaments. Even though there have been many studies on tensin as an adaptor protein, the role of tensin during development has not yet been clearly elucidated. The developmental role of tensin was dissected by isolating Drosophila tensin mutants and characterizing its role in wing development. The Drosophila tensin loss-of-function mutations resulted in the formation of blisters on the wings, due to a defective wing unfolding process. Interestingly, by¹ -- the mutant allele of the gene blistery (by) -- also shows a blistered wing phenotype, but fails to complement the wing blister phenotype of the Drosophila tensin mutants, implying that they are alleles of the same gene. These results demonstrate that by encodes Drosophila tensin protein and that the Drosophila tensin mutants are alleles of by. Using a genetic approach, it has been demonstrated that tensin interacts with integrin and also with the components of the JNK signaling pathway during wing development; overexpression of by in wing imaginal discs significantly increases JNK activity and induces apoptotic cell death. Collectively, these data suggest that tensin relays signals from the extracellular matrix to the cytoskeleton through interaction with integrin, and through the modulation of the JNK signal transduction pathway during Drosophila wing development (Lee, 2003).

Discs lost

Drosophila gene discs lost (dlt) has been reported to encode a homolog of the vertebrate tight junction PDZ protein Patj, and was thought to play a role in cell polarity (Bhat, 1999). Using rescue experiments and sequence analyses, dlt mutations have been shown to disrupt the Drosophila Codanin-1 homolog, a cytoplasmic protein, and not the PDZ protein. Mutations in human Codanin-1 are associated with congenital dyserythropoietic anemia type I (CDA I). In Drosophila, the genomic organization of dlt is unusual. dlt shares its first untranslated exon with α-spectrin, and both genes are coexpressed throughout development. dlt is not required for cell polarity but is needed for cell survival and cell cycle progression. Finally, evidence suggests that the PDZ protein previously thought to be encoded by dlt is not required for viability. It is proposed that PDZ protein be named after its vertebrate homolog, Patj (Pals-associated tight junction protein) (Pielage, 2003).

Dicer-2

RNA silencing phenomena, either the regulation of mRNA translation or regulation of mRNA degradation, intersect at the ribonuclease Dicer. In animals, the double-stranded RNA-specific endonuclease Dicer produces two classes of functionally distinct, tiny RNAs: microRNAs (miRNAs) and small interfering RNAs (siRNAs). miRNAs regulate mRNA translation, whereas siRNAs direct RNA destruction via the RNA interference (RNAi) pathway. siRNAs and miRNAs then direct a RNA-induced silencing complex (RISC) to cleave mRNA or block its translation (RNAi). Mutations have been characterized in the Drosophila dicer-1 and dicer-2 genes. Mutation in dicer-1 blocks processing of micro RNA precursors, whereas dicer-2 mutants are defective for processing siRNA precursors. It has been recently found that Drosophila Dicer-1 and Dicer-2 are also components of siRNA-dependent RISC (siRISC). Dicer-1 and Dicer-2 are required for siRNA-directed mRNA cleavage, though the RNase III activity of Dicer-2 is not required. Dicer-1 and Dicer-2 facilitate distinct steps in the assembly of siRISC. However, Dicer-1 (but not Dicer-2) is essential for miRISC-directed translation repression. Thus, siRISCs and miRISCs are different with respect to Dicers in Drosophila (Lee, 2004).

Grip

The Drosophila homolog of vertebrate Glutamate Receptor-Interacting Proteins (DGrip; FlyBase name -- Grip) acts as a key component of proper muscle guidance. Mutations in Grip impair patterning of ventral longitudinal muscles (VLMs), whereas lateral transverse muscles (LTMs) that attach to intrasegmental attachment sites develop normally. Myoblast fusion, stabilization of muscle contacts, and general muscle function are not impaired in the absence of Grip. Instead, the proper formation of cellular extensions during guidance fails in Grip mutant VLMs. Grip protein concentrates at the ends of VLMs while these muscles guide toward segment border attachment sites. Conversely, LTMs overexpressing Grip form ectopic cellular extensions that can cause attachment of these muscles to other muscles at segment borders. The data suggest that Grip participates in the reception of an attractive signal that emanates from the epidermal attachment sites to direct the motility of developing muscles. This Grip phenotype should provide a valuable means to study mechanistic principles of Grip function (Swan, 2004).

Lachesin

Organ morphogenesis requires the coordinated activity of many mechanisms involved in cell rearrangements, size control, cell proliferation and organ integrity. Lachesin (Lac), a cell surface protein, is required for the proper morphogenesis of the Drosophila tracheal system. Homozygous embryos for Lac mutations, which fail to complement the previous identified bulbous (bulb) mutation, display convoluted tracheal tubes and tube breaks. At the cellular level, enlarged cells are detected, suggesting that Lac regulates organ size by influencing cell length rather than cell number, and cell detachments, indicating a role for Lac in cell adhesion. Results from an in vitro assay further support that Lac behaves as a homophilic cell adhesion molecule. Lac co-localizes with Septate Junction (SJ) proteins, and ultrastructural analysis confirms that it accumulates specifically at this type of cellular junction. In Lac mutant embryos, previously characterized components of the SJs are mislocalized, indicating that the proper organization of SJs requires Lac function. In addition, mutations in genes encoding other components of the SJs produce a similar tracheal phenotype. These results point out a new role of the SJs in morphogenesis regulating cell adhesion and cell size (Llamargas, 2004).

Nervous wreck

nwk (nervous wreck), a temperature-sensitive paralytic mutant, causes excessive growth of larval neuromuscular junctions (NMJs), resulting in increased synaptic bouton number and branch formation. Ultrastructurally, mutant boutons have reduced size and fewer active zones, associated with a reduction in synaptic transmission. nwk encodes an FCH and SH3 domain-containing adaptor protein that localizes to the periactive zone of presynaptic terminals and binds to the Drosophila ortholog of Wasp (Wsp), a key regulator of actin polymerization. wsp null mutants display synaptic overgrowth similar to nwk and enhance the nwk morphological phenotype in a dose-dependent manner. Evolutionarily, Nwk belongs to a previously undescribed family of adaptor proteins that includes the human srGAPs, which regulate Rho activity downstream of Robo receptors. It is proposed that Nwk controls synapse morphology by regulating actin dynamics downstream of growth signals in presynaptic terminals (Coyle, 2004).

Nuclear fallout

Cytokinesis requires a dramatic remodeling of the cortical cytoskeleton as well as membrane addition via vesicle fusion. The Drosophila pericentrosomal protein, Nuclear-fallout (Nuf), provides a link between these two remodeling processes. In nuf-derived embryos, actin remodeling and membrane recruitment during the initial stages of metaphase and cellular furrow formation are disrupted. Nuf is a homolog of arfophilin-2, an ADP ribosylation factor (ARF; see InterPro's ADP-ribosylation factor) effector that binds Rab11 (and Arf5) and influences recycling endosome (RE) organization. Nuf has been shown to be an important component of the RE; these phenotypes are a consequence of Nuf activities at the RE. Nuf exhibits extensive colocalization with Rab11, a key RE component implicated in vesicle targeting. Tests for protein interaction and the presence of a conserved Rab11-binding domain in Nuf demonstrate that Nuf and Rab11 physically associate. In addition, Nuf and Rab11 are mutually required for their localization to the RE. Embryos with reduced levels of Rab11 produce membrane recruitment and actin remodeling defects strikingly similar to nuf-derived embryos. These analyses support a common role for Nuf and Rab11 at the RE in membrane trafficking and actin remodeling during the initial stages of furrow formation. Membrane addition is mediated via endosomal-mediated membrane delivery to the site of furrow formation (Riggs, 2003).

Pickpocket

Coordination of rhythmic locomotion depends upon a precisely balanced interplay between central and peripheral control mechanisms. Although poorly understood, peripheral proprioceptive mechanosensory input is thought to provide information about body position for moment-to-moment modifications of central mechanisms mediating rhythmic motor output. Pickpocket1 (PPK1) is a Drosophila subunit of the epithelial sodium channel (ENaC) family displaying limited expression in multiple dendritic (md) sensory neurons tiling the larval body wall and a small number of bipolar neurons in the upper brain (Adams, 1998). ppk1 null mutant larvae have normal external touch sensation and md neuron morphology but display striking alterations in crawling behavior. Loss of PPK1 function causes an increase in crawling speed and an unusual straight path with decreased stops and turns relative to wild-type. This enhanced locomotion results from sustained peristaltic contraction wave cycling at higher frequency with a significant decrease in pause period between contraction cycles. The mutant phenotype is rescued by a wild-type PPK1 transgene and duplicated by expressing a ppk1RNAi transgene or a dominant-negative PPK1 isoform. These results demonstrate that the Ppk1 channel plays an essential role in controlling rhythmic locomotion by providing mechanosensory signal transduction of proprioceptive sensory information (Ainsley, 2003).

Pyramus and Thisbe

The Heartless (Htl) FGF receptor is required for the differentiation of a variety of mesodermal tissues in the Drosophila embryo, yet its ligand is not known. Two FGF genes, thisbe (ths; FGF8-like1) and pyramus (pyr; FGF8-like2), have been identified that probably encode the elusive ligands for this receptor. The two genes were named for the 'heartbroken' lovers described in Ovid's Metamorphoses because the genes are linked and the mutant phenotype exhibits a lack of heart. The genes exhibit dynamic patterns of expression in epithelial tissues adjacent to Htl-expressing mesoderm derivatives, including the neurogenic ectoderm, stomadeum, and hindgut. Embryos that lack ths⁺ and pyr⁺ exhibit defects related to those seen in htl mutants, including delayed mesodermal migration during gastrulation and a loss of cardiac tissues and hindgut musculature. The misexpression of Ths in wild-type and mutant embryos suggests that FGF signaling is required for both cell migration and the transcriptional induction of cardiac gene expression. The characterization of htl and ths regulatory DNAs indicates that high levels of the maternal Dorsal gradient directly activates htl expression, whereas low levels activate ths. It is therefore possible to describe FGF signaling and other aspects of gastrulation as a direct manifestation of discrete threshold readouts of the Dorsal gradient (Stathopoulos, 2004; Gryzik, 2004).

Similar

In mammalian systems, the heterodimeric basic helix-loop-helix (bHLH)-PAS transcription hypoxia-inducible factor (HIF) has emerged as the key regulator of responses to decreased oxygen concentrations (reviewed by Semenza, 2001; see also Kaelin, 2002; Bruick, 2003; Bracken, 2003; Bruick, 2004). A homologous system is present in Drosophila, and its activity has been characterized in vivo during development. By using transcriptional reporters in developing transgenic flies, it has been shown that hypoxia-inducible activity rises to a peak in late embryogenesis and is most pronounced in tracheal cells. The bHLH-PAS proteins Similar (Sima) and Tango (Tgo) function as HIF-alpha and HIF-ß homologs, respectively; a conserved mode of regulation for Sima by oxygen has been demonstrated. Sima protein, but not its mRNA, is upregulated in hypoxia. Time course experiments following pulsed ectopic expression demonstrate that Sima is stabilized in hypoxia and that degradation relies on a central domain encompassing amino acids 692 to 863. Continuous ectopic expression overrode Sima degradation, which remains cytoplasmic in normoxia, and translocates to the nucleus only in hypoxia, revealing a second oxygen-regulated activation step. Abrogation of the Drosophila Egl-9 prolyl hydroxylase homolog, CG1114, causes both stabilization and nuclear localization of Sima, indicating a central involvement in both processes. Tight conservation of the HIF/prolyl hydroxylase system in Drosophila provides a new focus for understanding oxygen homeostasis in intact multicellular organisms (Lavista-Llanos, 2002).

Slow as molasses

Cellularization of the Drosophila embryo is a specialized form of cytokinesis that couples membrane growth with the formation of a polarized epithelium. slow as molasses (slam) is essential for polarized growth of the plasma membrane during cellularization. In slam mutant embryos, the furrow canal is disorganized, and polarized insertion of transmembrane proteins is disrupted. slam shows a striking developmental induction during the slow phase of cellularization, and Slam protein localizes to the furrow canal and the basal junction. Slam colocalizes with the junctional proteins Armadillo/ß-catenin, the PDZ domain-containing protein Dlt (renamed Patj), and Myosin (see Zipper) and is also required for their proper membrane localization. These results suggest that developmental induction of Slam organizes the polarized growth of membrane via the recruitment of membrane-targeting proteins at adherens junctions (Lecuit, 2002 and Stein, 2002).

Tollo

Specific glycan expression is an essential characteristic of developing tissues. Molecular characterization of a mutation in Tollo that abolishes neural-specific glycosylation in the Drosophila embryo demonstrates that cellular interactions influence glycan expression. The HRP epitope is an N-linked oligosaccharide expressed on a subset of neuronal glycoproteins. In wild-type embryos, Tollo is expressed by ectodermal cells that surround differentiating neurons and precedes HRP-epitope appearance. Re-introduction of Tollo into null embryos rescues neural-specific glycan expression. Thus, loss of an ectodermal cell surface protein alters glycosylation in juxtaposed differentiating neurons. Neural differentiation and axon extension, to the extent that they are revealed by standard monoclonal antibody markers, are unaffected by loss of Tollo function. The ability to induce specific glycan expression complements the previously identified developmental and innate immune functions of Toll-like receptors (Seppo, 2003).

Zero population growth

Germ cells require intimate associations and signals from the surrounding somatic cells throughout gametogenesis. The zero population growth (zpg) locus of Drosophila encodes a germline-specific gap junction protein, Innexin 4, that is required for survival of differentiating early germ cells during gametogenesis in both sexes. Animals with a null mutation in zpg are viable but sterile and have tiny gonads. Adult zpg-null gonads contain small numbers of early germ cells, resembling stem cells or early spermatogonia or oogonia, but lack later stages of germ cell differentiation. In the male, Zpg protein localizes to the surface of spermatogonia, primarily on the sides adjacent to the somatic cyst cells. In the female, Zpg protein localizes to germ cell surfaces, both those adjacent to surrounding somatic cells and those adjacent to other germ cells. It is proposed that Zpg-containing gap junctional hemichannels in the germ cell plasma membrane may connect with hemichannels made of other innexin isoforms on adjacent somatic cells. Gap junctional intercellular communication via these channels may mediate passage of crucial small molecules or signals between germline and somatic support cells required for survival and differentiation of early germ cells in both sexes (Tazuke, 2002).

What's new in this edition [40] April 2004 continues:

Updates for previously included genes:
part 2/5 genes A-E | part 3/5 genes F-M | part 4/5 genes N-R | part 5/5 genes S-Z

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