Genomes and Genes
Gene Symbol: fra
Alias: CG8581, CT24981, DCC, Dmel\CG8581, Fra, frazzled, CG8581-PA, CG8581-PB, CG8581-PC, DCC/Frazzled, Netrin-receptor, deleted in colorectal cancer, deleted in colorectal carcinoma, fra-PA, fra-PB, fra-PC
Species: fruit fly
- Bashaw G, Hu H, Nobes C, Goodman C. A novel Dbl family RhoGEF promotes Rho-dependent axon attraction to the central nervous system midline in Drosophila and overcomes Robo repulsion. J Cell Biol. 2001;155:1117-22 pubmed..Surprisingly, evidence from genetic, biochemical, and cell culture experiments suggests that the promotion of axon attraction by GEF64C is dependent on the activation of Rho, but not Rac or Cdc42. ..
- Rajagopalan S, Vivancos V, Nicolas E, Dickson B. Selecting a longitudinal pathway: Robo receptors specify the lateral position of axons in the Drosophila CNS. Cell. 2000;103:1033-45 pubmed..Local cues further refine the lateral position. Together, these long- and short-range guidance cues allow growth cones to select with precision a specific longitudinal pathway. ..
- Hummel T, Schimmelpfeng K, Klämbt C. Commissure formation in the embryonic CNS of Drosophila. Development. 1999;126:771-9 pubmed..Here we present evidence that beside the previously known NETRIN/FRAZZLED (DCC) signalling system an additional attractive system(s) is operating in the developing embryonic nervous ..
- Dorsten J, Kolodziej P, VanBerkum M. Frazzled regulation of myosin II activity in the Drosophila embryonic CNS. Dev Biol. 2007;308:120-32 pubmedb>Frazzled (Fra) is a chemoattractive guidance receptor regulating the cytoskeletal dynamics underlying growth cone steering at the Drosophila embryonic midline...
- Brierley D, Blanc E, Reddy O, Vijayraghavan K, Williams D. Dendritic targeting in the leg neuropil of Drosophila: the role of midline signalling molecules in generating a myotopic map. PLoS Biol. 2009;7:e1000199 pubmed publisher..of motoneuron dendrites in the leg neuropil is controlled by the midline signalling systems Slit-Robo and Netrin-Fra. These results reveal that dendritic targeting plays a major role in the formation of myotopic maps and suggests ..
- Hiramoto M, Hiromi Y, Giniger E, Hotta Y. The Drosophila Netrin receptor Frazzled guides axons by controlling Netrin distribution. Nature. 2000;406:886-9 pubmedNetrin is a secreted protein that can act as a chemotropic axon guidance cue. Two classes of Netrin receptor, DCC and UNC-5 (refs 6-9), are required for axon guidance and are thought to mediate Netrin signals in growth cones through ..
- Garbe D, Bashaw G. Independent functions of Slit-Robo repulsion and Netrin-Frazzled attraction regulate axon crossing at the midline in Drosophila. J Neurosci. 2007;27:3584-92 pubmed..and vertebrate systems support the idea that Netrin, secreted by midline cells, signals through DCC (Deleted in Colorectal Carcinoma)/UNC40/Frazzled receptors to attract commissural axons toward and across the midline, whereas Slit ..
- Winberg M, Mitchell K, Goodman C. Genetic analysis of the mechanisms controlling target selection: complementary and combinatorial functions of netrins, semaphorins, and IgCAMs. Cell. 1998;93:581-91 pubmed..Rather, these growth cones assess the relative balance of attractive and repulsive forces and select their targets based on the combinatorial and simultaneous input of multiple cues. ..
- Tripodi M, Evers J, Mauss A, Bate M, Landgraf M. Structural homeostasis: compensatory adjustments of dendritic arbor geometry in response to variations of synaptic input. PLoS Biol. 2008;6:e260 pubmed publisher..The growing arbor thus counterbalances naturally occurring variations in synaptic density and activity so as to ensure that an appropriate level of input is achieved. ..
- Furrer M, Kim S, Wolf B, Chiba A. Robo and Frazzled/DCC mediate dendritic guidance at the CNS midline. Nat Neurosci. 2003;6:223-30 pubmed..Using single-cell labeling, we describe specific guidance defects in dendrites of identified neurons in frazzled, robo, netrin and commissureless mutant embryos of Drosophila melanogaster...
- Manhire Heath R, Golenkina S, Saint R, Murray M. Netrin-dependent downregulation of Frazzled/DCC is required for the dissociation of the peripodial epithelium in Drosophila. Nat Commun. 2013;4:2790 pubmed publisher..promotes the survival of metastasized cells by inhibiting the pro-apoptotic effects of its receptor Deleted in Colorectal Carcinoma (DCC)...
- Mauss A, Tripodi M, Evers J, Landgraf M. Midline signalling systems direct the formation of a neural map by dendritic targeting in the Drosophila motor system. PLoS Biol. 2009;7:e1000200 pubmed publisher..We show that the midline signalling systems Slit/Robo and Netrin/Frazzled are the main molecular mechanisms that underlie dendritic targeting with respect to the midline...
- Al Anzi B, Wyman R. The Drosophila immunoglobulin gene turtle encodes guidance molecules involved in axon pathfinding. Neural Dev. 2009;4:31 pubmed publisher..The latter two capabilities are required by migrating axons to explore densely packed targets. ..
- Yang L, Garbe D, Bashaw G. A frazzled/DCC-dependent transcriptional switch regulates midline axon guidance. Science. 2009;324:944-7 pubmed publisher..Slit-roundabout repulsion and netrin-deleted in colorectal cancer (DCC) (frazzled) attraction must be tightly regulated to control midline axon guidance in vertebrates ..
- von Hilchen C, Hein I, Technau G, Altenhein B. Netrins guide migration of distinct glial cells in the Drosophila embryo. Development. 2010;137:1251-62 pubmed publisher..We further show that early Netrin-dependent guidance of LG requires expression of the receptor Frazzled (Fra) already in the precursor cell...
- Newquist G, Drennan J, Lamanuzzi M, Walker K, Clemens J, Kidd T. Blocking apoptotic signaling rescues axon guidance in Netrin mutants. Cell Rep. 2013;3:595-606 pubmed publisher..In contrast to the traditional role of Netrin as simply a guidance cue, our results demonstrate that guidance and survival activities may be functionally related. ..
- Fan X, Labrador J, Hing H, Bashaw G. Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline. Neuron. 2003;40:113-27 pubmed..These results provide a direct physical link between the Robo receptor and an important cytoskeletal regulatory protein complex and suggest that Rac can function in both attractive and repulsive axon guidance. ..
- Keleman K, Rajagopalan S, Cleppien D, Teis D, Paiha K, Huber L, et al. Comm sorts robo to control axon guidance at the Drosophila midline. Cell. 2002;110:415-27 pubmed..Axon traffic at the CNS midline is thus controlled by the intracellular trafficking of the Robo guidance receptor, which in turn depends on the precisely regulated expression of the Comm sorting receptor. ..
- VanZomeren Dohm A, Sarro J, Flannery E, Duman Scheel M. The Drosophila Netrin receptor frazzled/DCC functions as an invasive tumor suppressor. BMC Dev Biol. 2011;11:41 pubmed publisherLoss of heterozygosity at 18q, which includes the Deleted in Colorectal Cancer (DCC) gene, has been linked to many human cancers. However, it is unclear if loss of DCC is the specific underlying cause of these cancers...
- Keleman K, Dickson B. Short- and long-range repulsion by the Drosophila Unc5 netrin receptor. Neuron. 2001;32:605-17 pubmed..Here we report the identification of the Drosophila Unc5 receptor, and show that it is a repulsive Netrin receptor likely to contribute to motor axon guidance...
- Andrews G, Tanglao S, Farmer W, Morin S, Brotman S, Berberoglu M, et al. Dscam guides embryonic axons by Netrin-dependent and -independent functions. Development. 2008;135:3839-48 pubmed publisher..Netrin and Dscam mutants display dose sensitive interactions, suggesting that Dscam could act as a Netrin receptor. We show using cell overlay assays that Netrin binds to fly and vertebrate Dscam, and that Dscam binds Netrin ..
- Brenman J, Gao F, Jan L, Jan Y. Sequoia, a tramtrack-related zinc finger protein, functions as a pan-neural regulator for dendrite and axon morphogenesis in Drosophila. Dev Cell. 2001;1:667-77 pubmed
- Bashaw G, Goodman C. Chimeric axon guidance receptors: the cytoplasmic domains of slit and netrin receptors specify attraction versus repulsion. Cell. 1999;97:917-26 pubmedFrazzled (Fra) is the DCC-like Netrin receptor in Drosophila that mediates attraction; Roundabout (Robo) is a Slit receptor that mediates repulsion...
- Gong Q, Rangarajan R, Seeger M, Gaul U. The netrin receptor frazzled is required in the target for establishment of retinal projections in the Drosophila visual system. Development. 1999;126:1451-6 pubmed..Our data suggest that Frazzled does not function as a Netrin receptor in attracting retinal fibers to the target; nor does it seem to act as a homotypic cell adhesion molecule...
- Grueber W, Jan Y. Dendritic development: lessons from Drosophila and related branches. Curr Opin Neurobiol. 2004;14:74-82 pubmed..Here, we review some recent advances in our understanding of dendritic development in insects, focusing primarily on insights that have been gained from studies of Drosophila. ..
- Hiramoto M, Hiromi Y. ROBO directs axon crossing of segmental boundaries by suppressing responsiveness to relocalized Netrin. Nat Neurosci. 2006;9:58-66 pubmed..of the longitudinal axons is guided by Netrin, which is localized on commissural axons by its receptor, Frazzled. The Netrin cue on the commissure of the next segment can act as a barrier to longitudinal axons, inhibiting ..
- Kim Y, Fritz J, Seneviratne A, VanBerkum M. Constitutively active myosin light chain kinase alters axon guidance decisions in Drosophila embryos. Dev Biol. 2002;249:367-81 pubmed..Overexpression of Frazzled, the receptor for midline attractive Netrins, enhances ctMLCK-dependent crossovers, but crossovers are suppressed ..
- Grueber W, Yang C, Ye B, Jan Y. The development of neuronal morphology in insects. Curr Biol. 2005;15:R730-8 pubmed..We speculate about how and why the actions of these genes might facilitate the diversification of dendritic morphology. ..
- Timofeev K, Joly W, Hadjieconomou D, Salecker I. Localized netrins act as positional cues to control layer-specific targeting of photoreceptor axons in Drosophila. Neuron. 2012;75:80-93 pubmed publisher..We identified a central role for Netrins and their receptor Frazzled in mediating layer-specific axon targeting in the Drosophila visual system...
- Crews S. Control of cell lineage-specific development and transcription by bHLH-PAS proteins. Genes Dev. 1998;12:607-20 pubmed
- Simionato E, Barrios N, Duloquin L, Boissonneau E, Lecorre P, Agnès F. The Drosophila RNA-binding protein ELAV is required for commissural axon midline crossing via control of commissureless mRNA expression in neurons. Dev Biol. 2007;301:166-77 pubmed..Finally, forced expression of comm in specific commissural neuron subsets rescues the midline crossing defects of these neurons in elav mutant embryos, further indicating that elav acts cell autonomously on comm expression. ..
- Song H, Poo M. Signal transduction underlying growth cone guidance by diffusible factors. Curr Opin Neurobiol. 1999;9:355-63 pubmed..Furthermore, many diffusible guidance cues appear to share common cytoplasmic signaling pathways. ..
- Chiba A, Rose D. "Painting" the target: how local molecular cues define synaptic relationships. Bioessays. 1998;20:941-8 pubmed..In this review, we summarize how such studies are beginning to uncover the repertoire of extrinsic cues that influence the synaptic targeting of a single growth cone. ..
- Tear G. Axon guidance at the central nervous system midline. Cell Mol Life Sci. 1999;55:1365-76 pubmed..In this way, axons extend toward or away from the midline and those that do cross change their behaviour to respond to longitudinal signals on the contralateral side. ..
- Lu W, Casanueva M, Mahowald A, Kato M, Lauterbach D, Ferguson E. Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells. PLoS Biol. 2012;10:e1001357 pubmed publisher..We suggest that all adult stem cells likely employ multiple, independently acting mechanisms to ensure asymmetric division to maintain tissue homeostasis. ..
- Gupta T, Kumar A, Cattenoz P, Vijayraghavan K, Giangrande A. The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled. elife. 2016;5: pubmed publisher..Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing...
- Sarro J, Andrews E, Sun L, Behura S, Tan J, Zeng E, et al. Requirement for commissureless2 function during dipteran insect nerve cord development. Dev Dyn. 2013;242:1466-77 pubmed publisher..aegypti and D. melanogaster was found to result in loss of commissure defects that phenocopy the frazzled (fra) loss of function phenotypes observed in both species...
- Macabenta F, Jensen A, Cheng Y, Kramer J, Kramer S. Frazzled/DCC facilitates cardiac cell outgrowth and attachment during Drosophila dorsal vessel formation. Dev Biol. 2013;380:233-42 pubmed publisher..Here we provide genetic evidence that Netrin signals through DCC (Deleted in Colorectal Carcinoma)/UNC-40/Frazzled (Fra) to mediate CB outgrowth and attachment and that this function occurs prior to ..
- Gupta T, Giangrande A. Collective cell migration: "all for one and one for all". J Neurogenet. 2014;28:190-8 pubmed publisher..This review impinges upon the cellular and molecular interactions underlying collective cell migration in animal models, and highlights the recent advances made through in vivo analyses of the Drosophila wing glia. ..
- Hakeda Suzuki S, Suzuki T. Cell surface control of the layer specific targeting in the Drosophila visual system. Genes Genet Syst. 2014;89:9-15 pubmed..Fundamental and comprehensive understanding of the crosstalk of growing axons and target regions in the Drosophila optic lobe will elucidate the general principles applicable to more complex nervous systems. ..
- Organisti C, Hein I, Grunwald Kadow I, Suzuki T. Flamingo, a seven-pass transmembrane cadherin, cooperates with Netrin/Frazzled in Drosophila midline guidance. Genes Cells. 2015;20:50-67 pubmed publisher..In Drosophila, commissural axons sense the midline attractants Netrin A and B (Net) through Frazzled (Fra) receptors...
- Neuhaus Follini A, Bashaw G. The Intracellular Domain of the Frazzled/DCC Receptor Is a Transcription Factor Required for Commissural Axon Guidance. Neuron. 2015;87:751-63 pubmed publisherIn commissural neurons of Drosophila, the conserved Frazzled (Fra)/Deleted in Colorectal Cancer (DCC) receptor promotes midline axon crossing by signaling locally in response to Netrin and by inducing transcription of commissureless (comm)..
- Hsouna A, VanBerkum M. Abelson tyrosine kinase and Calmodulin interact synergistically to transduce midline guidance cues in the Drosophila embryonic CNS. Int J Dev Neurosci. 2008;26:345-54 pubmed publisher..Axons cross the midline in almost every segment if Frazzled is co-overexpressed with the Calmodulin inhibitor, but the crossovers induced by the Calmodulin inhibitor itself ..
- Ratnaparkhi A, Banerjee S, Hasan G. Altered levels of Gq activity modulate axonal pathfinding in Drosophila. J Neurosci. 2002;22:4499-508 pubmed..Analysis of the AcGq3 phenotype in roundabout and frazzled mutants shows that AcGq3 function is antagonistic to Robo signaling and requires Frazzled to promote ectopic ..
- Terman J, Kolodkin A. Attracted or repelled? Look within. Neuron. 1999;23:193-5 pubmed
- Long H, Yoshikawa S, Thomas J. Equivalent Activities of Repulsive Axon Guidance Receptors. J Neurosci. 2016;36:1140-50 pubmed publisher..We went on to show that this common pathway involves Trio, a guanine nucleotide exchange factor known to promote cytoskeletal remodeling. ..
- Kuzina I, Song J, Giniger E. How Notch establishes longitudinal axon connections between successive segments of the Drosophila CNS. Development. 2011;138:1839-49 pubmed publisher..This propels the axons as they establish the connection between successive segments. ..
- Akin O, Zipursky S. Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system. elife. 2016;5: pubmed publisher..The ligand-receptor pair, Netrin (Net) and Frazzled (Fra) (DCC, Deleted in Colorectal Cancer, in vertebrates), is recognized as the prototypical effector of chemoattraction, with roles in both ..
- Evans T, Santiago C, Arbeille E, Bashaw G. Robo2 acts in trans to inhibit Slit-Robo1 repulsion in pre-crossing commissural axons. elife. 2015;4:e08407 pubmed publisher..These findings indicate that at least two independent mechanisms to overcome Slit-Robo1 repulsion in pre-crossing commissural axons have evolved in Drosophila. ..
- Song S, Ge Q, Wang J, Chen H, Tang S, Bi J, et al. TRIM-9 functions in the UNC-6/UNC-40 pathway to regulate ventral guidance. J Genet Genomics. 2011;38:1-11 pubmed publisher..Over-expression of the Netrin/UNC-6 receptor Frazzled suppresses the guidance defects in trim-9 mutants...
- Carrillo R, Olsen D, Yoon K, Keshishian H. Presynaptic activity and CaMKII modulate retrograde semaphorin signaling and synaptic refinement. Neuron. 2010;68:32-44 pubmed publisher..These results indicate a role for patterned electrical activity and presynaptic calcium signaling, acting through CaMKII, in modulating a retrograde signal during the refinement of synaptic connections. ..
- Tear G. Neuronal guidance. A genetic perspective. Trends Genet. 1999;15:113-8 pubmed..Here I highlight the part genetic screens and analyses have played in revealing some of the key players in neuronal guidance. ..
- Blader -. Oh, for some simple guidance. Trends Genet. 2000;16:486 pubmed
- Dorsten J, Varughese B, Karmo S, Seeger M, VanBerkum M. In the absence of frazzled over-expression of Abelson tyrosine kinase disrupts commissure formation and causes axons to leave the embryonic CNS. PLoS ONE. 2010;5:e9822 pubmed publisherIn the Drosophila embryonic nerve cord, the formation of commissures require both the chemoattractive Netrin receptor Frazzled (Fra) and the Abelson (Abl) cytoplasmic tyrosine kinase...
- Koushika S, Soller M, White K. The neuron-enriched splicing pattern of Drosophila erect wing is dependent on the presence of ELAV protein. Mol Cell Biol. 2000;20:1836-45 pubmed..Additionally, we report that ELAV promotes a neuron-enriched splice isoform of Drosophila armadillo transcript. ELAV, however, is not involved in all neuron-enriched splice events. ..
- Giger R, Kolodkin A. Frazzled precision guides axons. Nature. 2000;406:841, 843 pubmed
- Mrkusich E, Osman Z, Bates K, Marchingo J, Duman Scheel M, Whitington P. Netrin-guided accessory cell morphogenesis dictates the dendrite orientation and migration of a Drosophila sensory neuron. Development. 2010;137:2227-35 pubmed publisher..The netrin receptor Frazzled is required for normal cap cell morphogenesis, and mutant rescue experiments indicate that it acts ..
- Drescher U. Netrins find their receptor. Nature. 1996;384:416-7 pubmed
- Ricolo D, ButÃ E, AraÃºjo S. Drosophila melanogaster Hedgehog cooperates with Frazzled to guide axons through a non-canonical signalling pathway. Mech Dev. 2015;137:11-22 pubmed publisher..Our results reveal that the Hh pathway cooperates with the Netrin/Frazzled pathway to guide axons through the midline in invertebrates.
- Couch J, Condron B. Axon guidance: Comm hither, Robo. Curr Biol. 2002;12:R741-2 pubmed..Recent studies have shed new light on the mechanism by which commissural axons change their sensitivity to guidance cues after crossing the midline. ..
- Pert M, Gan M, Saint R, Murray M. Netrins and Frazzled/DCC promote the migration and mesenchymal to epithelial transition of Drosophila midgut cells. Biol Open. 2015;4:233-43 pubmed publisher..are expressed in the visceral mesoderm, the substrate upon which midgut cells migrate, while their receptor frazzled (fra) is expressed in midgut cells...
- Onel S, Bolke L, Klämbt C. The Drosophila ARF6-GEF Schizo controls commissure formation by regulating Slit. Development. 2004;131:2587-94 pubmed..We thus propose that the balance of the two signaling cues Netrin and Slit can be regulated, controlling membrane dynamics. ..
- Brose K, Tessier Lavigne M. Slit proteins: key regulators of axon guidance, axonal branching, and cell migration. Curr Opin Neurobiol. 2000;10:95-102 pubmed
- Kolesnikov T, Beckendorf S. NETRIN and SLIT guide salivary gland migration. Dev Biol. 2005;284:102-11 pubmed..We propose that analogous to axon guidance, a balance between chemo-attractants and chemo-repellents is required for the proper migratory path of the developing salivary glands. ..
- Patel B, Van Vactor D. Axon guidance: the cytoplasmic tail. Curr Opin Cell Biol. 2002;14:221-9 pubmed..Recent studies demonstrate a critical role for the cytoplasmic tails of guidance receptors in signalling and also reveal the potential for a great deal of crosstalk between the various receptor-signalling pathways. ..
- Chotard C, Salecker I. Neurons and glia: team players in axon guidance. Trends Neurosci. 2004;27:655-61 pubmed..Equally, neurons provide crucial information to glia, supporting their migration and correct positioning. ..
- Kuang B, Wu S, Shin Y, Luo L, Kolodziej P. split ends encodes large nuclear proteins that regulate neuronal cell fate and axon extension in the Drosophila embryo. Development. 2000;127:1517-29 pubmed..We propose that Spen proteins regulate the expression of key effectors of signaling pathways required to specify neuronal cell fate and morphology. ..
- Packard M, Mathew D, Budnik V. FASt remodeling of synapses in Drosophila. Curr Opin Neurobiol. 2003;13:527-34 pubmed..These studies offer convincing evidence that synaptic cell adhesion brings about both negative and positive forces that stabilize synapses, while maintaining their ability to change in an activity-dependent manner. ..
- Liu Q, Hiramoto M, Ueda H, Gojobori T, Hiromi Y, Hirose S. Midline governs axon pathfinding by coordinating expression of two major guidance systems. Genes Dev. 2009;23:1165-70 pubmed publisher..Drosophila T-box protein Midline controls expression of genes encoding components of two major guidance systems: Frazzled, ROBO, and Slit...
- Coleman H, Labrador J, Chance R, Bashaw G. The Adam family metalloprotease Kuzbanian regulates the cleavage of the roundabout receptor to control axon repulsion at the midline. Development. 2010;137:2417-26 pubmed publisher..Finally, Kuz activity is required for Robo to recruit its downstream signaling partner, Son of sevenless (Sos). These observations support the model that Kuz-directed cleavage is important for Robo receptor activation. ..
- Couton L, Mauss A, Yunusov T, Diegelmann S, Evers J, Landgraf M. Development of connectivity in a motoneuronal network in Drosophila larvae. Curr Biol. 2015;25:568-76 pubmed publisher..Synapse number and the likelihood of forming connections appear to be regulated on a cell-by-cell basis, determined primarily by the postsynaptic dendrites of motoneuron terminals. ..
- Govek E, Newey S, Van Aelst L. The role of the Rho GTPases in neuronal development. Genes Dev. 2005;19:1-49 pubmed..This review will focus on the role of the Rho GTPases and their associated signaling molecules throughout neuronal development and discuss how perturbations in Rho GTPase signaling may lead to cognitive disorders. ..