Gene Symbol: how
Description: held out wings
Alias: 0904/17, 24B, CG10293, Dmel\CG10293, HOW, How, KH93F, P62, SZ1, Who/How, anon-EST:Liang-2.39, clone 2.39, l(3)S053606, l(3)S090417, l(3)j5B5, l(3)j5D5, l(3)s2612, qkr, qkr[93F], sci, stru, who, held out wings, CG10293-PA, CG10293-PB, CG10293-PC, CG10293-PD, CG10293-PE, CG10293-PF, Held-out wings, KH motif at 93F, held Out wing, how-PA, how-PB, how-PC, how-PD, how-PE, how-PF, lethal (3) S053606, lethal (3) S090417, quaking related, 93F, scorpion, struthio, wings held out, wings held-out
Species: fruit fly

Top Publications

  1. Zaffran S, Astier M, Gratecos D, Semeriva M. The held out wings (how) Drosophila gene encodes a putative RNA-binding protein involved in the control of muscular and cardiac activity. Development. 1997;124:2087-98 pubmed
    ..This gene has been named held out wings (how) because hypomorphic mutant alleles produce adult animals that have lost their ability to fly and that ..
  2. Rodrigues F, Thuma L, Klämbt C. The regulation of glial-specific splicing of Neurexin IV requires HOW and Cdk12 activity. Development. 2012;139:1765-76 pubmed publisher
    ..Here, we show that the formation of the BBB depends on the RNA-binding protein HOW (Held out wings), which triggers glial specific splicing of Neurexin IV(exon3)...
  3. Israeli D, Nir R, Volk T. Dissection of the target specificity of the RNA-binding protein HOW reveals dpp mRNA as a novel HOW target. Development. 2007;134:2107-14 pubmed
    ..The Drosophila RNA-binding protein Held out wing (HOW), regulates an array of developmental processes in embryonic and adult growth...
  4. Baehrecke E. who encodes a KH RNA binding protein that functions in muscle development. Development. 1997;124:1323-32 pubmed
    The Drosophila who (wings held-out) gene functions during the late stages of somatic muscle development when myotubes migrate and attach to specific epidermal sites...
  5. Nabel Rosen H, Volohonsky G, Reuveny A, Zaidel Bar R, Volk T. Two isoforms of the Drosophila RNA binding protein, how, act in opposing directions to regulate tendon cell differentiation. Dev Cell. 2002;2:183-93 pubmed
    ..This mechanism is based on the opposing activities of two isoforms of the RNA binding protein How. While the isoform How(L) is a negative regulator of Stripe, the key modulator of tendon cell differentiation, How(..
  6. Subramanian A, Prokop A, Yamamoto M, Sugimura K, Uemura T, Betschinger J, et al. Shortstop recruits EB1/APC1 and promotes microtubule assembly at the muscle-tendon junction. Curr Biol. 2003;13:1086-95 pubmed
    ..To address how Shot exerts its activity at the molecular level, we investigated the molecular interactions of Shot with candidate ..
  7. Nabel Rosen H, Toledano Katchalski H, Volohonsky G, Volk T. Cell divisions in the drosophila embryonic mesoderm are repressed via posttranscriptional regulation of string/cdc25 by HOW. Curr Biol. 2005;15:295-302 pubmed
    ..Here, we show that the repressor isoform of the Drosophila RNA binding protein Held Out Wing [HOW(L)] is required to inhibit mesodermal cell division during gastrulation...
  8. Monk A, Siddall N, Volk T, Fraser B, Quinn L, McLaughlin E, et al. HOW is required for stem cell maintenance in the Drosophila testis and for the onset of transit-amplifying divisions. Cell Stem Cell. 2010;6:348-60 pubmed publisher
    ..Here we demonstrate that the HOW RNA-binding protein is required for maintenance of CycB and therefore mitotic progression in GSCs and gonialblasts ..
  9. Volohonsky G, Edenfeld G, Klämbt C, Volk T. Muscle-dependent maturation of tendon cells is induced by post-transcriptional regulation of stripeA. Development. 2007;134:347-56 pubmed
    ..This elevation is mediated by the RNA-binding protein How(S), with levels sensitive to muscle-dependent signals...

More Information


  1. Bökel C, Brown N. Integrins in development: moving on, responding to, and sticking to the extracellular matrix. Dev Cell. 2002;3:311-21 pubmed
    ..Integrins also participate in signaling events that govern tissue differentiation and organogenesis. Finally, adhesion by integrin-mediated junctions allows tissues to withstand mechanical load and is essential for tissue integrity. ..
  2. Edenfeld G, Volohonsky G, Krukkert K, Naffin E, Lammel U, Grimm A, et al. The splicing factor crooked neck associates with the RNA-binding protein HOW to control glial cell maturation in Drosophila. Neuron. 2006;52:969-80 pubmed
    ..Within the cytoplasm, Crn interacts with the RNA-binding protein HOW and then translocates to the nucleus where the Crn/HOW complex controls glial differentiation by facilitating ..
  3. Nabel Rosen H, Dorevitch N, Reuveny A, Volk T. The balance between two isoforms of the Drosophila RNA-binding protein how controls tendon cell differentiation. Mol Cell. 1999;4:573-84 pubmed
    ..Here we show that the balance between two distinct forms of the RNA-binding protein How maintains low levels of Stripe at the precursor stage and high levels in the mature tendon...
  4. Reuveny A, Elhanany H, Volk T. Enhanced sensitivity of midline glial cells to apoptosis is achieved by HOW(L)-dependent repression of Diap1. Mech Dev. 2009;126:30-41 pubmed publisher
    ..Here, we show that the long isoform of the RNA-binding protein Held Out Wing (HOW(L)) is essential for enhancing the sensitivity of the MG cells to PCD...
  5. Vernet C, Artzt K. STAR, a gene family involved in signal transduction and activation of RNA. Trends Genet. 1997;13:479-84 pubmed
    ..It is hypothesized that these bifunctional proteins provide a rich source of interesting molecular information about development and define a new cellular pathway that links signal transduction directly to RNA metabolism. ..
  6. Lo P, Frasch M. A novel KH-domain protein mediates cell adhesion processes in Drosophila. Dev Biol. 1997;190:241-56 pubmed
    ..We have cloned and characterized a gene (struthio) that is expressed in embryonic mesodermal and muscle cells, including cardioblasts, and epidermal muscle ..
  7. Fyrberg C, Becker J, Barthmaier P, Mahaffey J, Fyrberg E. A Drosophila muscle-specific gene related to the mouse quaking locus. Gene. 1997;197:315-23 pubmed
    We have characterized a novel muscle-specific gene of Drosophila melanogaster, defined by enhancer trap strain 24B of Brand and Perrimon (1993)...
  8. Prout M, Damania Z, Soong J, Fristrom D, Fristrom J. Autosomal mutations affecting adhesion between wing surfaces in Drosophila melanogaster. Genetics. 1997;146:275-85 pubmed
    ..Mutations in three other genes (kakapo, kiwi and moa) may also affect cell adhesion or muscle function at hatching. These new mutants provide valuable material for the study of integrin-dependent cell-to-cell adhesion. ..
  9. Taylor M. Developmental biology: micromanaging muscle growth. Curr Biol. 2006;16:R20-3 pubmed
    ..Recently, the conserved microRNA miR-1 has been found to be essential for Drosophila development. miR-1 mutants die during the rapid larval growth phase with severe muscle defects. ..
  10. König A, Shcherbata H. Visualization of adult stem cells within their niches using the Drosophila germline as a model system. Methods Mol Biol. 2013;1035:25-33 pubmed publisher
    ..Two to three adult stem cells are surrounded by a number of somatic cells that form the niche. Here we describe how Drosophilae germaria can be dissected and specifically immuno-stained to allow for identification and analysis of ..
  11. Wu M, Joiner W, Dean T, Yue Z, Smith C, Chen D, et al. SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker. Nat Neurosci. 2010;13:69-75 pubmed publisher
    ..SSS is predicted to belong to the Ly-6/neurotoxin superfamily, suggesting a mechanism for regulation of neuronal excitability by endogenous toxin-like molecules. ..
  12. Suster M, Martin J, Sung C, Robinow S. Targeted expression of tetanus toxin reveals sets of neurons involved in larval locomotion in Drosophila. J Neurobiol. 2003;55:233-46 pubmed
    ..The results presented here provide a basis for future genetic studies of motor control in the Drosophila larva. ..
  13. Fyrberg C, Becker J, Barthmaier P, Mahaffey J, Fyrberg E. A family of Drosophila genes encoding quaking-related maxi-KH domains. Biochem Genet. 1998;36:51-64 pubmed
    We recently identified a Drosophila gene, wings held out (who), that specifies a STAR (signal transduction and RNA activation) protein expressed within mesoderm and muscles...
  14. Bulchand S, Menon S, George S, Chia W. Muscle wasted: a novel component of the Drosophila histone locus body required for muscle integrity. J Cell Sci. 2010;123:2697-707 pubmed publisher
    ..Importantly, Drosophila Myocyte enhancer factor 2 (Mef2), a central myogenic differentiation factor, and how, an RNA binding protein required for muscle and tendon cell differentiation, are downregulated...
  15. Di Fruscio M, Chen T, Bonyadi S, Lasko P, Richard S. The identification of two Drosophila K homology domain proteins. Kep1 and SAM are members of the Sam68 family of GSG domain proteins. J Biol Chem. 1998;273:30122-30 pubmed
    ..We demonstrate that SAM, KEP1, and the recently identified Drosophila Who/How are RNA-binding proteins that are able to self-associate into homomultimers...
  16. Nir R, Grossman R, Paroush Z, Volk T. Phosphorylation of the Drosophila melanogaster RNA-binding protein HOW by MAPK/ERK enhances its dimerization and activity. PLoS Genet. 2012;8:e1002632 pubmed publisher
    Drosophila melanogaster Held Out Wings (HOW) is a conserved RNA-binding protein (RBP) belonging to the STAR family, whose closest mammalian ortholog Quaking (QKI) has been implicated in embryonic development and nervous system myelination...
  17. Monk A, Siddall N, Fraser B, McLaughlin E, Hime G. Differential roles of HOW in male and female Drosophila germline differentiation. PLoS ONE. 2011;6:e28508 pubmed publisher
    ..The HOW RNA-binding protein has been shown to maintain mitotic progression of male GSCs and their daughters by maintenance ..
  18. Graindorge A, Carré C, Gebauer F. Sex-lethal promotes nuclear retention of msl2 mRNA via interactions with the STAR protein HOW. Genes Dev. 2013;27:1421-33 pubmed publisher
    ..a two-step purification method termed GRAB (GST pull-down and RNA affinity binding) and identified Held-Out-Wings (HOW) as a component of the msl2 5' UTR-associated complex...
  19. Lee H, Frasch M. Wingless effects mesoderm patterning and ectoderm segmentation events via induction of its downstream target sloppy paired. Development. 2000;127:5497-508 pubmed
    ..We also propose that in wg-expressing ectodermal cells, slp is an integral component in an autocrine feedback loop of Wg signaling. ..
  20. Grammont M, Irvine K. fringe and Notch specify polar cell fate during Drosophila oogenesis. Development. 2001;128:2243-53 pubmed
    ..Our results indicate that fringe plays a key role in positioning Notch activation during early oogenesis, and establish a function for the polar cells in separating germline cysts into individual follicles. ..
  21. Assa Kunik E, Torres I, Schejter E, Johnston D, Shilo B. Drosophila follicle cells are patterned by multiple levels of Notch signaling and antagonism between the Notch and JAK/STAT pathways. Development. 2007;134:1161-9 pubmed
  22. Giuliani G, Giuliani F, Volk T, Rabouille C. The Drosophila RNA-binding protein HOW controls the stability of dgrasp mRNA in the follicular epithelium. Nucleic Acids Res. 2014;42:1970-86 pubmed publisher
    ..two putative HOW Response Elements (HRE1 and HRE2) within the dgrasp open reading frame for binding to Held Out Wings (HOW), a member of the Signal Transduction and Activation of RNA family of RNA-binding proteins...
  23. Schulze S, Curio Penny B, Speese S, Dialynas G, Cryderman D, McDonough C, et al. A comparative study of Drosophila and human A-type lamins. PLoS ONE. 2009;4:e7564 pubmed publisher
    ..These studies provide new insights on the role of lamins in nuclear biology and support Drosophila as a model for studies of human laminopathies involving muscle dysfunction. ..
  24. van der Plas M, Pilgram G, Plomp J, de Jong A, Fradkin L, Noordermeer J. Dystrophin is required for appropriate retrograde control of neurotransmitter release at the Drosophila neuromuscular junction. J Neurosci. 2006;26:333-44 pubmed
    ..Our results indicate that the postsynaptically localized scaffolding protein Dystrophin is required for appropriate control of neuromuscular synaptic homeostasis. ..
  25. Carmon A, Topbas F, Baron M, MacIntyre R. dumpy interacts with a large number of genes in the developing wing of Drosophila melanogaster. Fly (Austin). 2010;4:117-27 pubmed
    ..Dumpy also interacts strongly with held out wings, which is involved in RNA localization and possibly alternative splicing.
  26. Jiang H, Edgar B. EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors. Development. 2009;136:483-93 pubmed publisher
    ..Two stronger EGFR ligands, Spitz and Keren, are expressed by the AMPs themselves and provide an additional, autocrine mitogenic stimulus to the AMPs during late larval stages. ..
  27. Fortier T, Chatterjee R, Klinedinst S, Baehrecke E, Woodard C. How functions in leg development during Drosophila metamorphosis. Dev Dyn. 2006;235:2248-59 pubmed
    The Drosophila how gene encodes a KH RNA binding protein with strong similarity to GLD-1 from nematodes and QK1 from mice. Here, we investigate the function of how during metamorphosis...
  28. Ryu J, Najand N, Brook W. Tinman is a direct activator of midline in the Drosophila dorsal vessel. Dev Dyn. 2011;240:86-95 pubmed publisher
    ..Mutation of two Tinman binding sites (Tin1 and Tin2) reduces or abolishes cardiac expression in derivatives of the 1.7 kb fragment. We conclude that Tin is a direct regulator of midline in fly heart development. ..
  29. Coulson M, Robert S, Saint R. Drosophila starvin encodes a tissue-specific BAG-domain protein required for larval food uptake. Genetics. 2005;171:1799-812 pubmed
    ..Our study provides the first report of an essential, developmentally regulated BAG-family gene. ..
  30. Allen M, O Kane C, Moffat K. Cell ablation using wild-type and cold-sensitive ricin-A chain in Drosophila embryonic mesoderm. Genesis. 2002;34:132-4 pubmed
  31. Marquez R, Singer M, Takaesu N, Waldrip W, Kraytsberg Y, Newfeld S. Transgenic analysis of the Smad family of TGF-beta signal transducers in Drosophila melanogaster suggests new roles and new interactions between family members. Genetics. 2001;157:1639-48 pubmed
    ..Overall, the study demonstrates that transgenic methods in Drosophila can provide new information about non-Drosophila members of developmentally important multigene families. ..
  32. González Castillo C, Ortuño Sahagún D, Guzmán Brambila C, Pallàs M, Rojas Mayorquín A. Pleiotrophin as a central nervous system neuromodulator, evidences from the hippocampus. Front Cell Neurosci. 2014;8:443 pubmed publisher
    ..In this paper, we summarize, discuss, and contrast the most recent advances and results that lead to proposing a PTN as a neuromodulatory molecule in the CNS, particularly in hippocampus. ..
  33. Dutta D, Buchon N, Xiang J, Edgar B. Regional Cell Specific RNA Expression Profiling of FACS Isolated Drosophila Intestinal Cell Populations. Curr Protoc Stem Cell Biol. 2015;34:2F.2.1-14 pubmed publisher
    ..This method will be useful for quantitative transcriptome comparison across intestinal cell types in the different regions under normal and various experimental conditions. ..
  34. Ji Y, Tulin A. Poly(ADP-Ribosyl)ation of hnRNP A1 Protein Controls Translational Repression in Drosophila. Mol Cell Biol. 2016;36:2476-86 pubmed publisher
    ..We conclude that Hrp38 represses Nanos translation, whereas its poly(ADP-ribosyl)ation relieves the repression effect, allowing restricted Nanos expression in the posterior germ plasm during oogenesis and early embryogenesis. ..
  35. Patel U, Davies S, Myat M. Receptor-type guanylyl cyclase Gyc76C is required for development of the Drosophila embryonic somatic muscle. Biol Open. 2012;1:507-15 pubmed publisher
    ..These studies provide the first evidence for a requirement for Gyc76C and DG1 in Drosophila somatic muscle development, and suggest a role in transport and/or retention of integrin receptor subunits at the developing MTJs. ..
  36. Clavier A, Baillet A, Rincheval Arnold A, Coléno Costes A, Lasbleiz C, Mignotte B, et al. The pro-apoptotic activity of Drosophila Rbf1 involves dE2F2-dependent downregulation of diap1 and buffy mRNA. Cell Death Dis. 2014;5:e1405 pubmed publisher
    ..On the other hand, Rbf1 and dE2F2 upregulate how expression. How is a RNA binding protein involved in diap1 mRNA degradation...
  37. Zappia M, Frolov M. E2F function in muscle growth is necessary and sufficient for viability in Drosophila. Nat Commun. 2016;7:10509 pubmed publisher
    ..These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells.
  38. Nitabach M, Wu Y, Sheeba V, Lemon W, Strumbos J, Zelensky P, et al. Electrical hyperexcitation of lateral ventral pacemaker neurons desynchronizes downstream circadian oscillators in the fly circadian circuit and induces multiple behavioral periods. J Neurosci. 2006;26:479-89 pubmed
    ..Thus, regulated electrical activity of the LNVs synchronize multiple oscillators in the fly circadian pacemaker circuit. ..
  39. Zaffran S, Chartier A, Gallant P, Astier M, Arquier N, Doherty D, et al. A Drosophila RNA helicase gene, pitchoune, is required for cell growth and proliferation and is a potential target of d-Myc. Development. 1998;125:3571-84 pubmed
    ..These results suggest that myc might promote cell proliferation by activating genes that are required in protein biosynthesis, thus linking cell growth and cell proliferation. ..
  40. Walsh E, Brown N. A screen to identify Drosophila genes required for integrin-mediated adhesion. Genetics. 1998;150:791-805 pubmed
    ..Thus several of these loci are good candidates for genes encoding cytoplasmic proteins required for integrin function. ..
  41. Haye A, Albert J, Rooman M. Modeling the Drosophila gene cluster regulation network for muscle development. PLoS ONE. 2014;9:e90285 pubmed publisher
    ..The non-uniqueness of the solutions and the variable agreement with experimental connections were discussed in the context of the different hypotheses underlying this type of approach. ..
  42. Medioni C, Astier M, Zmojdzian M, Jagla K, Semeriva M. Genetic control of cell morphogenesis during Drosophila melanogaster cardiac tube formation. J Cell Biol. 2008;182:249-61 pubmed publisher
    ..Furthermore, we identify a genetic pathway in which roundabout, slit, held out wings, and dystroglycan control cardiac lumen formation by establishing nonadherent luminal membranes and regulating ..
  43. Kazemian M, Zhu Q, Halfon M, Sinha S. Improved accuracy of supervised CRM discovery with interpolated Markov models and cross-species comparison. Nucleic Acids Res. 2011;39:9463-72 pubmed publisher
    ..We make our program available as downloadable source code, and as a plugin for a genome browser installed on our servers. ..
  44. Chan H, Brogna S, O Kane C. Dribble, the Drosophila KRR1p homologue, is involved in rRNA processing. Mol Biol Cell. 2001;12:1409-19 pubmed
    ..Clonal analyses suggest that dbe(+) is required for survival of dividing cells. In dbe mutants, a novel rRNA-processing defect is found and accumulation of an abnormal rRNA precursor is detected. ..