Bioelectric Signaling Regulates Size in Zebrafish Fins
The scaling relationship between the size of an appendage or organ and that of the body as a whole is tightly regulated during animal development. If a structure grows at a different rate than the rest of the body, this process is termed allometric growth. The zebrafish another longfin (alf) mutant shows allometric growth resulting in proportionally enlarged fins and barbels. We took advantage of this mutant to study the regulation of size in vertebrates. Here, we show that alf mutants carry gain-of-function mutations in kcnk5b, a gene encoding a two-pore domain potassium (K+) channel. Electrophysiological analysis in Xenopus oocytes reveals that these mutations cause an increase in K+ conductance of the channel and lead to hyperpolarization of the cell. Further, somatic transgenesis experiments indicate that kcnk5b acts locally within the mesenchyme of fins and barbels to specify appendage size. Finally, we show that the channel requires the ability to conduct K+ ions to increase the size of these structures. Our results provide evidence for a role of bioelectric signaling through K+ channels in the regulation of allometric scaling and coordination of growth in the zebrafish.
Vyšlo v časopise:
Bioelectric Signaling Regulates Size in Zebrafish Fins. PLoS Genet 10(1): e32767. doi:10.1371/journal.pgen.1004080
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004080
Souhrn
The scaling relationship between the size of an appendage or organ and that of the body as a whole is tightly regulated during animal development. If a structure grows at a different rate than the rest of the body, this process is termed allometric growth. The zebrafish another longfin (alf) mutant shows allometric growth resulting in proportionally enlarged fins and barbels. We took advantage of this mutant to study the regulation of size in vertebrates. Here, we show that alf mutants carry gain-of-function mutations in kcnk5b, a gene encoding a two-pore domain potassium (K+) channel. Electrophysiological analysis in Xenopus oocytes reveals that these mutations cause an increase in K+ conductance of the channel and lead to hyperpolarization of the cell. Further, somatic transgenesis experiments indicate that kcnk5b acts locally within the mesenchyme of fins and barbels to specify appendage size. Finally, we show that the channel requires the ability to conduct K+ ions to increase the size of these structures. Our results provide evidence for a role of bioelectric signaling through K+ channels in the regulation of allometric scaling and coordination of growth in the zebrafish.
Zdroje
1. LuiJC, BaronJ (2011) Mechanisms limiting body growth in mammals. Endocr Rev 32: 422–440.
2. HuxleyJS, TeissierG (1936) Terminology of relative growth. Nature 137: 780–781.
3. GouldSJ (1966) Allometry and size in ontogeny and phylogeny. Biol Rev Camb Philos Soc 41: 587–640.
4. MetcalfD (1963) The autonomous behaviour of normal thymus grafts. Aust J Exp Biol Med Sci 41: SUPPL437–447.
5. MetcalfD (1964) Restricted growth capacity of multiple spleen grafts. Transplantation 2: 387–392.
6. ConlonI, RaffM (1999) Size Control in Animal Development. Cell 96: 235–244.
7. TwittyVC, SchwindJL (1931) The growth of eyes and limbs transplanted heteroplastically between two species of Amblystoma. Journal of Experimental Zoology 59: 61–86.
8. Ohki-HamazakiH, KatsumataT, TsukamotoY, WadaN, KimuraI (1997) Control of the limb bud outgrowth in quail-chick chimera. Dev Dyn 208: 85–91.
9. SchneiderRA, HelmsJA (2003) The cellular and molecular origins of beak morphology. Science 299: 565–568.
10. SengelP (1971) The organogenesis and arrangement of cutaneous appendages in birds. Adv Morphog 9: 181–230.
11. ZwillingE (1955) Ectoderm — mesoderm relationship in the development of the chick embryo limb bud. Journal of Experimental Zoology 128: 423–441.
12. HarveyKF, ZhangX, ThomasDM (2013) The Hippo pathway and human cancer. Nat Rev Cancer 13: 246–257.
13. TumanengK, RussellRC, GuanK-L (2012) Organ size control by Hippo and TOR pathways. Curr Biol 22: R368–379.
14. GoldsteinSA, BockenhauerD, O'KellyI, ZilberbergN (2001) Potassium leak channels and the KCNK family of two-P-domain subunits. Nat Rev Neurosci 2: 175–184.
15. TalleyEM, SiroisJE, LeiQ, BaylissDA (2003) Two-pore-Domain (KCNK) potassium channels: dynamic roles in neuronal function. Neuroscientist 9: 46–56.
16. LevinM (2007) Large-scale biophysics: ion flows and regeneration. Trends Cell Biol 17: 261–270.
17. AltizerAM, MoriartyLJ, BellSM, SchreinerCM, ScottWJ, et al. (2001) Endogenous electric current is associated with normal development of the vertebrate limb. Developmental Dynamics 221: 391–401.
18. BorgensRB, VanableJWJr, JaffeLF (1977) Bioelectricity and regeneration: large currents leave the stumps of regenerating newt limbs. Proc Natl Acad Sci U S A 74: 4528–4532.
19. KurtzI, SchrankAR (1955) Bioelectrical Properties of Intact and Regenerating Earthworms, Eisenia foetida. Physiological Zoology 28: 322–330.
20. BorgensRB, VanableJW, JaffeLF (1979) Small artificial currents enhance Xenopus limb regeneration. Journal of Experimental Zoology 207: 217–226.
21. TsengAS, BeaneWS, LemireJM, MasiA, LevinM (2010) Induction of vertebrate regeneration by a transient sodium current. J Neurosci 30: 13192–13200.
22. AdamsDS, MasiA, LevinM (2007) H+ pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration. Development 134: 1323–1335.
23. ReidB, SongB, ZhaoM (2009) Electric currents in Xenopus tadpole tail regeneration. Dev Biol 335: 198–207.
24. AdamsDS, TsengAS, LevinM (2013) Light-activation of the Archaerhodopsin H(+)-pump reverses age-dependent loss of vertebrate regeneration: sparking system-level controls in vivo. Biol Open 2: 306–313.
25. MorganTH (1900) Regeneration in teleosts. Arch Entwickslungsmech 10: 120–131.
26. GrandelH, Schulte-MerkerS (1998) The development of the paired fins in the zebrafish (Danio rerio). Mech Dev 79: 99–120.
27. GossRJ, StaggMW (1957) The regeneration of fins and fin rays in Fundulus heteroclitus. J Exp Zool 136: 487–507.
28. HaasHJ (1962) Studies on mechanisms of joint and bone formation in the skeleton rays of fish fins. Dev Biol 5: 1–34.
29. IovineMK (2007) Conserved mechanisms regulate outgrowth in zebrafish fins. Nat Chem Biol 3: 613–618.
30. van EedenFJ, GranatoM, SchachU, BrandM, Furutani-SeikiM, et al. (1996) Genetic analysis of fin formation in the zebrafish, Danio rerio. Development 123: 255–262.
31. FisherS, JagadeeswaranP, HalpernME (2003) Radiographic analysis of zebrafish skeletal defects. Dev Biol 264: 64–76.
32. GoldsmithMI, FisherS, WatermanR, JohnsonSL (2003) Saltatory control of isometric growth in the zebrafish caudal fin is disrupted in long fin and rapunzel mutants. Dev Biol 259: 303–317.
33. IovineMK, HigginsEP, HindesA, CoblitzB, JohnsonSL (2005) Mutations in connexin43 (GJA1) perturb bone growth in zebrafish fins. Dev Biol 278: 208–219.
34. HaffterP, OdenthalJr, MullinsMC, LinS, FarrellMJ, et al. (1996) Mutations affecting pigmentation and shape of the adult zebrafish. Development Genes and Evolution 206: 260–276.
35. HarrisMP, RohnerN, SchwarzH, PerathonerS, KonstantinidisP, et al. (2008) Zebrafish eda and edar mutants reveal conserved and ancestral roles of ectodysplasin signaling in vertebrates. PLoS Genet 4: e1000206.
36. SimsKJr, EbleDM, IovineMK (2009) Connexin43 regulates joint location in zebrafish fins. Dev Biol 327: 410–418.
37. IovineMK, JohnsonSL (2000) Genetic analysis of isometric growth control mechanisms in the zebrafish caudal Fin. Genetics 155: 1321–1329.
38. GreenJ, TaylorJJ, HindesA, JohnsonSL, GoldsmithMI (2009) A gain of function mutation causing skeletal overgrowth in the rapunzel mutant. Dev Biol 334: 224–234.
39. BrohawnSG, del MarmolJ, MacKinnonR (2012) Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel. Science 335: 436–441.
40. EnyediP, CzirjákG (2010) Molecular background of leak K+ currents: two-pore domain potassium channels. Physiol Rev 90: 559–605.
41. LesageF, LazdunskiM (2000) Molecular and functional properties of two-pore-domain potassium channels. Am J Physiol Renal Physiol 279: F793–801.
42. ClarkRB, KondoC, BelkeDD, GilesWR (2011) Two-pore domain K+ channels regulate membrane potential of isolated human articular chondrocytes. J Physiol 589: 5071–5089.
43. TuS, JohnsonSL (2011) Fate restriction in the growing and regenerating zebrafish fin. Dev Cell 20: 725–732.
44. LeClairEE, TopczewskiJ (2010) Development and regeneration of the zebrafish maxillary barbel: a novel study system for vertebrate tissue growth and repair. PLoS One 5: e8737.
45. KuzhikandathilEV, OxfordGS (2000) Dominant-negative mutants identify a role for GIRK channels in D3 dopamine receptor-mediated regulation of spontaneous secretory activity. J Gen Physiol 115: 697–706.
46. ShiehCC, CoghlanM, SullivanJP, GopalakrishnanM (2000) Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacol Rev 52: 557–594.
47. DahalGR, RawsonJ, GassawayB, KwokB, TongY, et al. (2012) An inwardly rectifying K+ channel is required for patterning. Development 139: 3653–3664.
48. Tristani-FirouziM, EtheridgeSP (2010) Kir 2.1 channelopathies: the Andersen-Tawil syndrome. Pflugers Arch 460: 289–294.
49. IwashitaM, WatanabeM, IshiiM, ChenT, JohnsonSL, et al. (2006) Pigment pattern in jaguar/obelix zebrafish is caused by a Kir7.1 mutation: implications for the regulation of melanosome movement. PLoS Genet 2: e197.
50. NiemeyerMI, CidLP, BarrosLF, SepúlvedaFV (2001) Modulation of the two-pore domain acid-sensitive K+ channel TASK-2 (KCNK5) by changes in cell volume. J Biol Chem 276: 43166–43174.
51. KirkegaardSS, LambertIH, GammeltoftS, HoffmannEK (2010) Activation of the TASK-2 channel after cell swelling is dependent on tyrosine phosphorylation. Am J Physiol Cell Physiol 299: C844–853.
52. SantariusT, BignellGR, GreenmanCD, WidaaS, ChenL, et al. (2010) GLO1-A novel amplified gene in human cancer. Genes Chromosomes Cancer 49: 711–725.
53. Alvarez-BaronCP, JonssonP, ThomasC, DryerSE, WilliamsC (2011) The two-pore domain potassium channel KCNK5: induction by estrogen receptor alpha and role in proliferation of breast cancer cells. Mol Endocrinol 25: 1326–1336.
54. WangZ (2004) Roles of K+ channels in regulating tumour cell proliferation and apoptosis. Pflugers Arch 448: 274–286.
55. BinggeliR, WeinsteinRC (1986) Membrane potentials and sodium channels: hypotheses for growth regulation and cancer formation based on changes in sodium channels and gap junctions. J Theor Biol 123: 377–401.
56. ChernetBT, LevinM (2013) Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model. Dis Model Mech 6: 595–607.
57. ConeCDJr (1971) Unified theory on the basic mechanism of normal mitotic control and oncogenesis. J Theor Biol 30: 151–181.
58. YangM, BrackenburyWJ (2013) Membrane potential and cancer progression. Front Physiol 4: 185.
59. PatelSK, JacksonL, WarrenAY, AryaP, ShawRW, et al. (2013) A role for two-pore potassium (K2P) channels in endometrial epithelial function. J Cell Mol Med 17: 134–146.
60. WonderlinWF, StroblJS (1996) Potassium channels, proliferation and G1 progression. J Membr Biol 154: 91–107.
61. BlackistonDJ, McLaughlinKA, LevinM (2009) Bioelectric controls of cell proliferation: ion channels, membrane voltage and the cell cycle. Cell Cycle 8: 3519–3528.
62. HegleAP, MarbleDD, WilsonGF (2006) A voltage-driven switch for ion-independent signaling by ether-à-go-go K+ channels. Proc Natl Acad Sci U S A 103: 2886–2891.
63. MillershipJE, DevorDC, HamiltonKL, BalutCM, BruceJIE, et al. (2011) Calcium-activated K+ channels increase cell proliferation independent of K+ conductance. Am J Physiol Cell Physiol 300: C792–802.
64. ZwillingE (1959) Interaction between Ectoderm and Mesoderm in Duck-Chicken Limb Bud Chimaeras. Journal of Experimental Zoology 142: 521–532.
65. FallonJF, KelleyRO (1977) Ultrastruct analysis of the apical ectodermal ridge duri;g vertebrate limb morphogenesis. II. Gap junctions as distinctive ridge structures common to birds and mammals. J Embryol Exp Morphol 41: 223–232.
66. FlennikenAM, OsborneLR, AndersonN, CilibertiN, FlemingC, et al. (2005) A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia. Development 132: 4375–4386.
67. MakarenkovaH, PatelK (1999) Gap junction signalling mediated through connexin-43 is required for chick limb development. Dev Biol 207: 380–392.
68. MurcianoC, Pérez-ClarosJ, SmithA, AvaronF, FernándezTD, et al. (2007) Position dependence of hemiray morphogenesis during tail fin regeneration in Danio rerio. Dev Biol 312: 272–283.
69. SchulteCJ, AllenC, EnglandSJ, Juárez-MoralesJL, LewisKE (2011) Evx1 is required for joint formation in zebrafish fin dermoskeleton. Dev Dyn 240: 1240–1248.
70. BeaneWS, MorokumaJ, LemireJM, LevinM (2013) Bioelectric signaling regulates head and organ size during planarian regeneration. Development 140: 313–322.
71. HermleT, SaltukogluD, GrunewaldJ, WalzG, SimonsM (2010) Regulation of Frizzled-dependent planar polarity signaling by a V-ATPase subunit. Curr Biol 20: 1269–1276.
72. HotaryKB, RobinsonKR (1992) Evidence of a role for endogenous electrical fields in chick embryo development. Development 114: 985–996.
73. PaiVP, AwS, ShomratT, LemireJM, LevinM (2012) Transmembrane voltage potential controls embryonic eye patterning in Xenopus laevis. Development 139: 313–323.
74. JenkinsLS, DuerstockBS, BorgensRB (1996) Reduction of the current of injury leaving the amputation inhibits limb regeneration in the red spotted newt. Dev Biol 178: 251–262.
75. ShiR, BorgensRB (1995) Three-dimensional gradients of voltage during development of the nervous system as invisible coordinates for the establishment of embryonic pattern. Dev Dyn 202: 101–114.
76. MetcalfMEM, ShiR, BorgensRB (1994) Endogenous ionic currents and voltages in amphibian embryos. Journal of Experimental Zoology 268: 307–322.
77. MarshG, BeamsHW (1952) Electrical control of morphogenesis in regenerating dugesia tigrina. I. Relation of axial polarity to field strength. Journal of Cellular and Comparative Physiology 39: 191–213.
78. OviedoNJ, MorokumaJ, WalentekP, KemaIP, GuMB, et al. (2010) Long-range neural and gap junction protein-mediated cues control polarity during planarian regeneration. Dev Biol 339: 188–199.
79. WatanabeM, IwashitaM, IshiiM, KurachiY, KawakamiA, et al. (2006) Spot pattern of leopard Danio is caused by mutation in the zebrafish connexin41.8 gene. EMBO Rep 7: 893–897.
80. WatanabeM, WatanabeD, KondoS (2012) Polyamine sensitivity of gap junctions is required for skin pattern formation in zebrafish. Sci Rep 2: 473.
81. InabaM, YamanakaH, KondoS (2012) Pigment pattern formation by contact-dependent depolarization. Science 335: 677.
82. Nüsslein-Volhard C, Dahm R (2002) Zebrafish: a practical approach. Oxford: Oxford University Press.
83. VandenplasS, WillemsM, HuysseuneA (2012) Dual BrdU-PCNA immunodetection of proliferative cells in dental and orofacial tissues of teleosts. Journal of Applied Ichthyology 28: 336–340.
84. HildebrandA, RemmertM, BiegertA, SödingJ (2009) Fast and accurate automatic structure prediction with HHpred. Proteins 77 Suppl 9: 128–132.
85. Strutz-SeebohmN, GutcherI, DecherN, SteinmeyerK, LangF, et al. (2007) Comparison of potent Kv1.5 potassium channel inhibitors reveals the molecular basis for blocking kinetics and binding mode. Cell Physiol Biochem 20: 791–800.
86. ZhengL, BaumannU, ReymondJ-L (2004) An efficient one-step site-directed and site-saturation mutagenesis protocol. Nucleic Acids Res 32: e115.
87. OviedoNJ, NicolasCL, AdamsDS, LevinM (2008) Live Imaging of Planarian Membrane Potential Using DiBAC4(3). CSH Protoc 2008 pdb prot5055.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2014 Číslo 1
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- GATA6 Is a Crucial Regulator of Shh in the Limb Bud
- Large Inverted Duplications in the Human Genome Form via a Fold-Back Mechanism
- Genome Sequencing Highlights the Dynamic Early History of Dogs
- Down-Regulation of Rad51 Activity during Meiosis in Yeast Prevents Competition with Dmc1 for Repair of Double-Strand Breaks