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Fat-Dachsous Signaling Coordinates Cartilage Differentiation and Polarity during Craniofacial Development


Little is known about the mechanisms of cell-cell communication necessary to assemble skeletal elements of appropriate size and shape. In this study, we investigate the roles of genetic factors belonging to a developmental pathway that affects skeletal progenitor behavior: the atypical cadherins Fat3 and Dachsous2 (Dchs2), and REREa/Atr2a. We show that cartilage precursors fail to rearrange into linear stacks and at the same time misregulate expression of sox9a, a key regulator of cartilage differentiation, in zebrafish embryos deficient in Fat3 or its partner Dchs2. Similar cartilage defects are observed in rerea−/− mutants, and Fat3 interacts physically and genetically with REREa. Our results suggest that Fat3, Dchs2 and REREa interact to control polarized cell-cell intercalation and simultaneously control skeletal differentiation through Sox9. By transplanting cartilage precursors between wild-type and Fat3, Dchs2 or REREa deficient embryos we demonstrate that all three factors exert long-range influences on neighboring cells, most likely mediated by another polarizing signal. We propose a model in which this coordinates the polarity and differentiation of chondrocytes to shape skeletal primordia, and that defects in these processes underlie human skeletal malformations.


Vyšlo v časopise: Fat-Dachsous Signaling Coordinates Cartilage Differentiation and Polarity during Craniofacial Development. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004726
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004726

Souhrn

Little is known about the mechanisms of cell-cell communication necessary to assemble skeletal elements of appropriate size and shape. In this study, we investigate the roles of genetic factors belonging to a developmental pathway that affects skeletal progenitor behavior: the atypical cadherins Fat3 and Dachsous2 (Dchs2), and REREa/Atr2a. We show that cartilage precursors fail to rearrange into linear stacks and at the same time misregulate expression of sox9a, a key regulator of cartilage differentiation, in zebrafish embryos deficient in Fat3 or its partner Dchs2. Similar cartilage defects are observed in rerea−/− mutants, and Fat3 interacts physically and genetically with REREa. Our results suggest that Fat3, Dchs2 and REREa interact to control polarized cell-cell intercalation and simultaneously control skeletal differentiation through Sox9. By transplanting cartilage precursors between wild-type and Fat3, Dchs2 or REREa deficient embryos we demonstrate that all three factors exert long-range influences on neighboring cells, most likely mediated by another polarizing signal. We propose a model in which this coordinates the polarity and differentiation of chondrocytes to shape skeletal primordia, and that defects in these processes underlie human skeletal malformations.


Zdroje

1. DoddsGS (1930) Row formation and other types of arrangement of cartilage cells in endochondral ossification. Anatomical Record 46: 385–399.

2. KimmelCB, MillerCT, KruzeG, UllmannB, BreMillerRA, et al. (1998) The shaping of pharyngeal cartilages during early development of the zebrafish. Developmental Biology 203: 245–263.

3. BiWM, DengJM, ZhangZP, BehringerRR, de CrombruggheB (1999) Sox9 is required for cartilage formation. Nature Genetics 22: 85–89.

4. YanYL, WilloughbyJ, LiuD, CrumpJG, WilsonC, et al. (2005) A pair of Sox: distinct and overlapping functions of zebrafish sox9 co-orthologs in craniofacial and pectoral fin development. Development 132: 1069–1083.

5. GrayRS, RoszkoI, Solnica-KrezelL (2011) Planar Cell Polarity: Coordinating Morphogenetic Cell Behaviors with Embryonic Polarity. Developmental Cell 21: 120–133.

6. AdlerPN (2002) Planar signaling and morphogenesis in Drosophila. Developmental Cell 2: 525–535.

7. HeisenbergCP, TadaM, RauchGJ, SaudeL, ConchaML, et al. (2000) Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature 405: 76–81.

8. KellerR, DavidsonL, EdlundA, ElulT, EzinM, et al. (2000) Mechanisms of convergence and extension by cell intercalation. Philosophical Transactions of the Royal Society B-Biological Sciences 355: 897–922.

9. WallingfordJB, RowningBA, VogeliKM, RothbacherU, FraserSE, et al. (2000) Dishevelled controls cell polarity during Xenopus gastrulation. Nature 405: 81–85.

10. CirunaB, JennyA, LeeD, MlodzikM, SchierAF (2006) Planar cell polarity signalling couples cell division and morphogenesis during neurulation. Nature 439: 220–224.

11. SaburiS, HesterI, FischerE, PontoglioM, EreminaV, et al. (2008) Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease. Nature Genetics 40: 1010–1015.

12. SepichDS, UsmaniM, PawlickiS, Solnica-KrezelL (2011) Wnt/PCP signaling controls intracellular position of MTOCs during gastrulation convergence and extension movements. Development 138: 543–552.

13. GaoB, SongH, BishopK, ElliotG, GarrettL, et al. (2011) Wnt Signaling Gradients Establish Planar Cell Polarity by Inducing Vangl2 Phosphorylation through Ror2. Developmental Cell 20: 163–176.

14. LawrencePA, StruhlG, CasalJ (2007) Planar cell polarity: one or two pathways? Nature Reviews Genetics 8: 555–563.

15. DevenportD, FuchsE (2008) Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nature Cell Biology 10: 1257–U1212.

16. LiYW, DudleyAT (2009) Noncanonical frizzled signaling regulates cell polarity of growth plate chondrocytes. Development 136: 1083–1092.

17. SaburiS, HesterI, GoodrichL, McNeillH (2012) Functional interactions between Fat family cadherins in tissue morphogenesis and planar polarity. Development 139: 1806–1820.

18. YangCH, AxelrodJD, SimonMA (2002) Regulation of Frizzled by fat-like cadherins during planar polarity signaling in the Drosophila compound eye. Cell 108: 675–688.

19. AdlerPN, CharltonJ, LiuJC (1998) Mutations in the cadherin superfamily member gene dachsous cause a tissue polarity phenotype by altering frizzled signaling. Development 125: 959–968.

20. FantoM, ClaytonL, MeredithJ, HardimanK, CharrouxB, et al. (2003) The tumor-suppressor and cell adhesion molecule Fat controls planar polarity via physical interactions with Atrophin, a transcriptional co-repressor. Development 130: 763–774.

21. ZeidlerMP, PerrimonN, StruttDI (1999) The four-jointed gene is required in the Drosophila eye for ommatidial polarity specification. Current Biology 9: 1363–1372.

22. BrittleAL, RepisoA, CasalJ, LawrencePA, StruttD (2010) Four-Jointed Modulates Growth and Planar Polarity by Reducing the Affinity of Dachsous for Fat. Current Biology 20: 803–810.

23. MatakatsuH, BlairSS (2004) Interactions between Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing. Development 131: 3785–3794.

24. SimonMA, XuAG, IshikawaHO, IrvineKD (2010) Modulation of Fat:Dachsous Binding by the Cadherin Domain Kinase Four-Jointed. Current Biology 20: 811–817.

25. ZoltewiczJS, StewartNJ, LeungR, PetersonAS (2004) Atrophin 2 recruits histone deacetylase and is required for the function of multiple signaling centers during mouse embryogenesis. Development 131: 3–14.

26. WangL, RajanH, PitmanJL, McKeownM, TsaiCC (2006) Histone deacetylase-associating Atrophin proteins are nuclear receptor corepressors. Genes & Development 20: 525–530.

27. CasalJ, StruhlG, LawrencePA (2002) Developmental compartments and planar polarity in Drosophila. Current Biology 12: 1189–1198.

28. SimonMA (2004) Planar cell polarity in the Drosophila eye is directed by graded four-jointed and Dachsous expression. Development 131: 6175–6184.

29. LawrencePA, StruhlG, CasalJ (2008) Do the protocadherins Fat and Dachsous link up to determine both planar cell polarity and the dimensions of organs? Nature Cell Biology 10: 1379–1382.

30. SharmaP, McNeillH (2013) Regulation of long-range planar cell polarity by Fat-Dachsous signaling. Development 140: 3869–3881.

31. SchillingTF, KimmelCB (1997) Musculoskeletal patterning in the pharyngeal segments of the zebrafish embryo. Development 124: 2945–2960.

32. SchillingTF, Le PabicP, HoffmanTL (2010) Using transgenic zebrafish (Danio rerio) to study development of the craniofacial skeleton. Journal of Applied Ichthyology 26: 183–186.

33. JonesC, RoperVC, FoucherI, QianD, BanizsB, et al. (2008) Ciliary proteins link basal body polarization to planar cell polarity regulation. Nature Genetics 40: 69–77.

34. ParkTJ, MitchellBJ, AbituaPB, KintnerC, WallingfordJB (2008) Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells. Nature Genetics 40: 871–879.

35. BorovinaA, SuperinaS, VoskasD, CirunaB (2010) Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia. Nature Cell Biology 12: 407–U242.

36. PlasterN, SonntagC, SchillingTF, HammerschmidtM (2007) REREa/Atrophin-2 interacts with histone deacetylase and Fgf8 signaling to regulate multiple processes of zebrafish development. Developmental Dynamics 236: 1891–1904.

37. PlasterN, SonntagC, BusseCE, HammerschmidtM (2006) p53 Deficiency rescues apoptosis and differentiation of multiple cell types in zebrafish flathead mutants deficient for zygotic DNA polymerase delta 1. Cell Death and Differentiation 13: 223–235.

38. RobuME, LarsonJD, NaseviciusA, BeiraghiS, BrennerC, et al. (2007) p53 activation by knockdown technologies. Plos Genetics 3: 787–801.

39. HouR, SibingaNES (2009) Atrophin Proteins Interact with the Fat1 Cadherin and Regulate Migration and Orientation in Vascular Smooth Muscle Cells. Journal of Biological Chemistry 284: 6955–6965.

40. JessenJR, TopczewskiJ, BinghamS, SepichDS, MarlowF, et al. (2002) Zebrafish trilobite identifies new roles for Strabismus in gastrulation and neuronal movements. Nature Cell Biology 4: 610–615.

41. YinC, KiskowskiM, PouilleP-A, FargeE, Solnica-KrezelL (2008) Cooperation of polarized cell intercalations drives convergence and extension of presomitic mesoderm during zebrafish gastrulation. Journal of Cell Biology 180: 221–232.

42. BiWM, HuangWD, WhitworthDJ, DengJM, ZhangZP, et al. (2001) Haploinsufficiency of Sox9 results in defective cartilage primordia and premature skeletal mineralization. Proceedings of the National Academy of Sciences of the United States of America 98: 6698–6703.

43. BellDM, LeungKKH, WheatleySC, NgLJ, ZhouS, et al. (1997) SOX9 directly regulates the type-II collagen gene. Nature Genetics 16: 174–178.

44. YvonAMC, WalkerJW, DanowskiB, FagerstromC, KhodjakovA, et al. (2002) Centrosome reorientation in wound-edge cells is cell type specific. Molecular Biology of the Cell 13: 1871–1880.

45. TanoueT, TakeichiM (2005) New insights into Fat cadherins. Journal of Cell Science 118: 2347–2353.

46. ViktorinovaI, KonigT, SchlichtingK, DahmannC (2009) The cadherin Fat2 is required for planar cell polarity in the Drosophila ovary. Development 136: 4123–4132.

47. StruttH, StruttD (2002) Nonautonomous planar polarity patterning in Drosophila: Dishevelled-independent functions of frizzled. Developmental Cell 3: 851–863.

48. MatakatsuH, BlairSS (2012) Separating planar cell polarity and Hippo pathway activities of the protocadherins Fat and Dachsous. Development 139: 1498–1508.

49. PanGH, FengYQ, AmbegaonkarAA, SunGP, HuffM, et al. (2013) Signal transduction by the Fat cytoplasmic domain. Development 140: 831–842.

50. DegoutinJL, MiltonCC, YuE, TippingM, BosveldF, et al. (2013) Riquiqui and Minibrain are regulators of the Hippo pathway downstream of Dachsous. Nat Cell Biol 15: 1176–1185.

51. TopczewskiJ, SepichDS, MyersDC, WalkerC, AmoresA, et al. (2001) The zebrafish glypican knypek controls cell polarity during gastrulation movements of convergent extension. Developmental Cell 1: 251–264.

52. PiotrowskiT, SchillingTF, BrandM, JiangYJ, HeisenbergCP, et al. (1996) Jaw and branchial arch mutants in zebrafish.2. Anterior arches and cartilage differentiation. Development 123: 345–356.

53. CooperMTD, BraySJ (1999) Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye. Nature 397: 526–530.

54. FantoM, MlodzikM (1999) Asymmetric Notch activation specifies photoreceptors R3 and R4 and planar polarity in the Drosophila eye. Nature 397: 523–526.

55. ZhengL, ZhangJJ, CarthewRW (1995) Frizzled regulates mirror-image symmetrical pattern-formation in the Drosophila eye. Development 121: 3045–3055.

56. WadaN, JavidanY, NelsonS, CarneyTJ, KelshRN, et al. (2005) Hedgehog signaling is required for cranial neural crest morphogenesis and chondrogenesis at the midline in the zebrafish skull. Development 132: 3977–3988.

57. CarneyTJ, DuttonKA, GreenhillE, Delfino-MachinM, DufourcqP, et al. (2006) A direct role for Sox10 in specification of neural crest-derived sensory neurons. Development 133: 4619–4630.

58. KimmelCB, BallardWW, KimmelSR, UllmannB, SchillingTF (1995) Stages of embryonic-development of the zebrafish. Developmental Dynamics 203: 253–310.

59. WuHH, IvkovicS, MurrayRC, JaramilloS, LyonsKM, et al. (2003) Autoregulation of neurogenesis by GDF11. Neuron 37: 197–207.

60. MuzumdarMD, TasicB, MiyamichiK, LiL, LuoL (2007) A global double-fluorescent Cre reporter mouse. Genesis 45: 593–605.

61. YanYL, HattaK, RigglemanB, PostlethwaitJH (1995) EXPRESSION OF A TYPE-II COLLAGEN GENE IN THE ZEBRAFISH EMBRYONIC AXIS. Developmental Dynamics 203: 363–376.

62. YanYL, MillerCT, NissenR, SingerA, LiuD, et al. (2002) A zebrafish sox9 gene required for cartilage morphogenesis. Development 129: 5065–5079.

63. Nagy A, Gertsenstein M, Vintersten K, Behringer R (2009) Alcian blue staining of the mouse fetal cartilaginous skeleton. Cold Spring Harb Protoc 2009: pdb prot5169.

64. ZhangS, XuL, LeeJ, XuT (2002) Drosophila atrophin homolog functions as a transcriptional corepressor in multiple developmental processes. Cell 108: 45–56.

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Genetika Reprodukčná medicína

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PLOS Genetics


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