Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway

English version České info

Mammary glands are the most characteristic feature of all mammals. The successful growth and function of the mammary glands is vital for the survival of offspring since the secreted milk is the main nutritional source of a new-born. Ectodysplasin (Eda) is a signaling molecule that regulates the formation of skin appendages such as hair, teeth, feathers, scales, and several glands in all vertebrates studied so far. In humans, mutations in the EDA gene cause a congenital disorder characterized by sparse hair, missing teeth, and defects in exocrine glands including the breast. We have previously shown that excess Eda induces formation of supernumerary mammary glands in mice. Here, we show that Eda leads to extra mammary gland formation also in the neck, a region previously not thought to harbor capacity to support mammary development. Using Eda loss- and gain-of-function mouse models and transcriptional profiling we identify the downstream mediators of Eda. The presence of extra nipples is a fairly common developmental abnormality in humans. We suggest that misregulation of Eda or its effectors might account for some of these malformations. Further, the number and location of the mammary glands vary widely between different species. Tinkering with the Eda pathway activity could provide an evolutionary means to modulate the number of mammary glands.

Vyšlo v časopise: Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway. PLoS Genet 11(11): e32767. doi:10.1371/journal.pgen.1005676
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005676

Souhrn

Zdroje

1. Propper AY, Howard BA, Veltmaat JM. (2013) Prenatal morphogenesis of mammary glands in mouse and rabbit. J Mammary Gland Biol Neoplasia 18(2): 93–104. doi: 10.1007/s10911-013-9298-0 23736987

2. Veltmaat JM, Van Veelen W, Thiery JP, Bellusci S. (2004) Identification of the mammary line in mouse by Wnt10b expression. Dev Dyn 229(2): 349–356. doi: 10.1002/dvdy.10441 14745960

3. Chu EY, Hens J, Andl T, Kairo A, Yamaguchi TP, et al. (2004) Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development 131(19): 4819–4829. doi: 10.1242/dev.01347 15342465

4. Mailleux AA, Spencer-Dene B, Dillon C, Ndiaye D, Savona-Baron C, et al. (2002) Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo. Development 129(1): 53–60. 11782400

5. Balinsky BI. (1950) On the prenatal growth of the mammary gland rudiment in the mouse. J Anat 84(3): 227–235. 15436328

6. Lee MY, Racine V, Jagadpramana P, Sun L, Yu W, et al. (2011) Ectodermal influx and cell hypertrophy provide early growth for all murine mammary rudiments, and are differentially regulated among them by Gli3. PLoS One 6(10): e26242. doi: 10.1371/journal.pone.0026242 22046263

7. Biggs LC, Mikkola ML. (2014) Early inductive events in ectodermal appendage morphogenesis. Semin Cell Dev Biol 25–26: 11–21. doi: 10.1016/j.semcdb.2014.01.007 24487243

8. Pispa J, Thesleff I. (2003) Mechanisms of ectodermal organogenesis. Dev Biol 262(2): 195–205. 14550785

9. Cowin P, Wysolmerski J. (2010) Molecular mechanisms guiding embryonic mammary gland development. Cold Spring Harb Perspect Biol.

10. Veltmaat JM, Relaix F, Le LT, Kratochwil K, Sala FG, et al. (2006) Gli3-mediated somitic Fgf10 expression gradients are required for the induction and patterning of mammary epithelium along the embryonic axes. Development 133(12): 2325–2335. 133/12/2325 [pii]. 16720875

11. Hatsell SJ, Cowin P. (2006) Gli3-mediated repression of hedgehog targets is required for normal mammary development. Development 133(18): 3661–3670. dev.02542 [pii]. 16914490

12. Davenport TG, Jerome-Majewska LA, Papaioannou VE. (2003) Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. Development 130(10): 2263–2273. 12668638

13. Eblaghie MC, Song SJ, Kim JY, Akita K, Tickle C, et al. (2004) Interactions between FGF and wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos. J Anat 205(1): 1–13. doi: 10.1111/j.0021-8782.2004.00309.x 15255957

14. Cho KW, Kim JY, Song SJ, Farrell E, Eblaghie MC, et al. (2006) Molecular interactions between Tbx3 and Bmp4 and a model for dorsoventral positioning of mammary gland development. Proc Natl Acad Sci U S A 103(45): 16788–16793. 0604645103 [pii]. 17071745

15. Howard B, Panchal H, McCarthy A, Ashworth A. (2005) Identification of the scaramanga gene implicates Neuregulin3 in mammary gland specification. Genes Dev 19(17): 2078–2090. 19/17/2078 [pii]. 16140987

16. Panchal H, Wansbury O, Parry S, Ashworth A, Howard B. (2007) Neuregulin3 alters cell fate in the epidermis and mammary gland. BMC Dev Biol 7: 105. 1471-213X-7-105 [pii]. 17880691

17. Mikkola ML. (2008) TNF superfamily in skin appendage development. Cytokine Growth Factor Rev 19(3–4): 219–230. doi: 10.1016/j.cytogfr.2008.04.008 18495521

18. Kowalczyk-Quintas C, Schneider P. (2014) Ectodysplasin A (EDA)—EDA receptor signalling and its pharmacological modulation. Cytokine Growth Factor Rev 25(2): 195–203. doi: 10.1016/j.cytogfr.2014.01.004 24508088

19. Schmidt-Ullrich R, Aebischer T, Hulsken J, Birchmeier W, Klemm U, et al. (2001) Requirement of NF-kappaB/rel for the development of hair follicles and other epidermal appendices. Development 128(19): 3843–3853. 11585809

20. Haara O, Fujimori S, Schmidt-Ullrich R, Hartmann C, Thesleff I, et al. (2011) Ectodysplasin and wnt pathways are required for salivary gland branching morphogenesis. Development 138(13): 2681–2691. doi: 10.1242/dev.057711 21652647

21. Clarke A, Phillips DI, Brown R, Harper PS. (1987) Clinical aspects of X-linked hypohidrotic ectodermal dysplasia. Arch Dis Child 62(10): 989–996. 2445301

22. Haghighi A, Nikuei P, Haghighi-Kakhki H, Saleh-Gohari N, Baghestani S, et al. (2013) Whole-exome sequencing identifies a novel missense mutation in EDAR causing autosomal recessive hypohidrotic ectodermal dysplasia with bilateral amastia and palmoplantar hyperkeratosis. Br J Dermatol 168(6): 1353–1356. doi: 10.1111/bjd.12151 23210707

23. Megarbane H, Cluzeau C, Bodemer C, Fraitag S, Chababi-Atallah M, et al. (2008) Unusual presentation of a severe autosomal recessive anhydrotic ectodermal dysplasia with a novel mutation in the EDAR gene. Am J Med Genet A 146A(20): 2657–2662. doi: 10.1002/ajmg.a.32509 18816645

24. Voutilainen M, Lindfors PH, Lefebvre S, Ahtiainen L, Fliniaux I, et al. (2012) Ectodysplasin regulates hormone-independent mammary ductal morphogenesis via NF-kappaB. Proc Natl Acad Sci U S A 109(15): 5744–5749. doi: 10.1073/pnas.1110627109 22451941

25. Pispa J, Pummila M, Barker PA, Thesleff I, Mikkola ML. (2008) Edar and troy signalling pathways act redundantly to regulate initiation of hair follicle development. Hum Mol Genet 17(21): 3380–3391. doi: 10.1093/hmg/ddn232 18689798

26. Mustonen T, Pispa J, Mikkola ML, Pummila M, Kangas AT, et al. (2003) Stimulation of ectodermal organ development by ectodysplasin-A1. Dev Biol 259(1): 123–136. 12812793

27. Mustonen T, Ilmonen M, Pummila M, Kangas AT, Laurikkala J, et al. (2004) Ectodysplasin A1 promotes placodal cell fate during early morphogenesis of ectodermal appendages. Development 131(20): 4907–4919. doi: 10.1242/dev.01377 15371307

28. Fliniaux I, Mikkola ML, Lefebvre S, Thesleff I. (2008) Identification of dkk4 as a target of eda-A1/edar pathway reveals an unexpected role of ectodysplasin as inhibitor of wnt signalling in ectodermal placodes. Dev Biol 320(1): 60–71. doi: 10.1016/j.ydbio.2008.04.023 18508042

29. Mahler B, Gocken T, Brojan M, Childress S, Spandau DF, et al. (2004) Keratin 2e: A marker for murine nipple epidermis. Cells Tissues Organs 176(4): 169–177. doi: 10.1159/000077033 15118396

30. Baud V, Karin M. (2009) Is NF-kappaB a good target for cancer therapy? hopes and pitfalls. Nat Rev Drug Discov 8(1): 33–40. doi: 10.1038/nrd2781 19116625

31. Narhi K, Tummers M, Ahtiainen L, Itoh N, Thesleff I, et al. (2012) Sostdc1 defines the size and number of skin appendage placodes. Dev Biol 364(2): 149–161. 22509524

32. Boras-Granic K, Hamel PA. (2013) Wnt-signalling in the embryonic mammary gland. J Mammary Gland Biol Neoplasia 18(2): 155–163. doi: 10.1007/s10911-013-9280-x 23660702

33. Jerome-Majewska LA, Jenkins GP, Ernstoff E, Zindy F, Sherr CJ, et al. (2005) Tbx3, the ulnar-mammary syndrome gene, and Tbx2 interact in mammary gland development through a p19Arf/p53-independent pathway. Dev Dyn 234(4): 922–933. doi: 10.1002/dvdy.20575 16222716

34. Zhang Y, Tomann P, Andl T, Gallant NM, Huelsken J, et al. (2009) Reciprocal requirements for EDA/EDAR/NF-kappaB and wnt/beta-catenin signaling pathways in hair follicle induction. Dev Cell 17(1): 49–61. doi: 10.1016/j.devcel.2009.05.011 19619491

35. Lefebvre S, Fliniaux I, Schneider P, Mikkola ML. (2012) Identification of ectodysplasin target genes reveals the involvement of chemokines in hair development. J Invest Dermatol 132(4): 1094–1102. doi: 10.1038/jid.2011.453 22277947

36. Wiseman BS, Sternlicht MD, Lund LR, Alexander CM, Mott J, et al. (2003) Site-specific inductive and inhibitory activities of MMP-2 and MMP-3 orchestrate mammary gland branching morphogenesis. J Cell Biol 162(6): 1123–1133. doi: 10.1083/jcb.200302090 12975354

37. Drogemuller C, Karlsson EK, Hytonen MK, Perloski M, Dolf G, et al. (2008) A mutation in hairless dogs implicates FOXI3 in ectodermal development. Science 321(5895): 1462. doi: 10.1126/science.1162525 18787161

38. Shirokova V, Jussila M, Hytonen MK, Perala N, Drogemuller C, et al. (2013) Expression of Foxi3 is regulated by ectodysplasin in skin appendage placodes. Dev Dyn 242(6): 593–603. doi: 10.1002/dvdy.23952 23441037

39. Mao B, Niehrs C. (2003) Kremen2 modulates Dickkopf2 activity during wnt/LRP6 signaling. Gene 302(1–2): 179–183. 12527209

40. de Lau WB, Snel B, Clevers HC. (2012) The R-spondin protein family. Genome Biol 13(3): 242-2012-13-3-242. doi: 10.1186/gb-2012-13-3-242 22439850

41. Carmon KS, Gong X, Lin Q, Thomas A, Liu Q. (2011) R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate wnt/beta-catenin signaling. Proc Natl Acad Sci U S A 108(28): 11452–11457. doi: 10.1073/pnas.1106083108 21693646

42. Weng J, Luo J, Cheng X, Jin C, Zhou X, et al. (2008) Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2. Proc Natl Acad Sci U S A 105(16): 6081–6086. doi: 10.1073/pnas.0708257105 18424556

43. Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, et al. (2006) Receptor specificity of the fibroblast growth factor family. the complete mammalian FGF family. J Biol Chem 281(23): 15694–15700. M601252200 [pii]. 16597617

44. Voutilainen M, Lindfors PH, Mikkola ML. (2013) Protocol: Ex vivo culture of mouse embryonic mammary buds. J Mammary Gland Biol Neoplasia 18(2): 239–245. doi: 10.1007/s10911-013-9288-2 23674216

45. Michno K, Boras-Granic K, Mill P, Hui CC, Hamel PA. (2003) Shh expression is required for embryonic hair follicle but not mammary gland development. Dev Biol 264(1): 153–165. S0012160603004019 [pii]. 14623238

46. Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, et al. (2009) Tankyrase inhibition stabilizes axin and antagonizes wnt signalling. Nature 461(7264): 614–620. doi: 10.1038/nature08356 19759537

47. Bianchi N, Depianto D, McGowan K, Gu C, Coulombe PA. (2005) Exploiting the keratin 17 gene promoter to visualize live cells in epithelial appendages of mice. Mol Cell Biol 25(16): 7249–7259. 25/16/7249 [pii]. 16055733

48. Rohrschneider LR, Custodio JM, Anderson TA, Miller CP, Gu H. (2005) The intron 5/6 promoter region of the ship1 gene regulates expression in stem/progenitor cells of the mouse embryo. Dev Biol 283(2): 503–521. S0012-1606(05)00270-8 [pii]. 15978570

49. Ahn Y, Sims C, Logue JM, Weatherbee SD, Krumlauf R. (2013) Lrp4 and wise interplay controls the formation and patterning of mammary and other skin appendage placodes by modulating wnt signaling. Development 140(3): 583–593. doi: 10.1242/dev.085118 23293290

50. Hehlgans T, Pfeffer K. (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: Players, rules and the games. Immunology 115(1): 1–20. IMM2143 [pii]. 15819693

51. Kumar A, Eby MT, Sinha S, Jasmin A, Chaudhary PM. (2001) The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A. J Biol Chem 276(4): 2668–2677. doi: 10.1074/jbc.M008356200 11035039

52. Fliniaux I, Mikkola ML, Lefebvre S, Thesleff I. (2008) Identification of dkk4 as a target of eda-A1/edar pathway reveals an unexpected role of ectodysplasin as inhibitor of wnt signalling in ectodermal placodes. Dev Biol 320(1): 60–71. doi: 10.1016/j.ydbio.2008.04.023 18508042

53. Kondo S, Miura T. (2010) Reaction-diffusion model as a framework for understanding biological pattern formation. Science 329(5999): 1616–1620. doi: 10.1126/science.1179047 20929839

54. Painter KJ, Hunt GS, Wells KL, Johansson JA, Headon DJ. (2012) Towards an integrated experimental-theoretical approach for assessing the mechanistic basis of hair and feather morphogenesis. Interface Focus 2(4): 433–450. doi: 10.1098/rsfs.2011.0122 23919127

55. Arte S, Parmanen S, Pirinen S, Alaluusua S, Nieminen P. (2013) Candidate gene analysis of tooth agenesis identifies novel mutations in six genes and suggests significant role for WNT and EDA signaling and allele combinations. PLoS One 8(8): e73705. doi: 10.1371/journal.pone.0073705 23991204

56. Cui CY, Yin M, Sima J, Childress V, Michel M, et al. (2014) Involvement of wnt, eda and shh at defined stages of sweat gland development. Development 141(19): 3752–3760. doi: 10.1242/dev.109231 25249463

57. Schmidt-Ullrich R, Tobin DJ, Lenhard D, Schneider P, Paus R, et al. (2006) NF-kappaB transmits eda A1/EdaR signalling to activate shh and cyclin D1 expression, and controls post-initiation hair placode down growth. Development 133(6): 1045–1057. dev.02278 [pii]. 16481354

58. Mohri Y, Kato S, Umezawa A, Okuyama R, Nishimori K. (2008) Impaired hair placode formation with reduced expression of hair follicle-related genes in mice lacking Lgr4. Dev Dyn 237(8): 2235–2242. doi: 10.1002/dvdy.21639 18651655

59. Wang Y, Dong J, Li D, Lai L, Siwko S, et al. (2013) Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2. Stem Cells 31(9): 1921–1931. doi: 10.1002/stem.1438 23712846

60. Bresslau E. (1920) The mammary apparatus of the mammalia: In the light of ontogenesis and phylogenesis. London: Methuen & Co.

61. Gilbert AN. (1986) Mammary number and litter size in rodentia: The "one-half rule". Proc Natl Acad Sci U S A 83(13): 4828–4830. 16593720

62. Veltmaat JM, Ramsdell AF, Sterneck E. (2013) Positional variations in mammary gland development and cancer. J Mammary Gland Biol Neoplasia 18(2): 179–188. doi: 10.1007/s10911-013-9287-3 23666389

63. Gifford W. (1934) The occurrence of polythelia in dairy cattle. Journal of Dairy Science 17(8): 559–569.

64. Lecompte E, Granjon L, Denys C. (2002) The phylogeny of the Praomys complex (rodentia: Muridae) and its phylogeographic implications. Journal of Zoological Systematics and Evolutionary Research 40(1): 8–25.

65. Kajava Y. (1915) The proportions of supernumerary nipples in the finnish population. Duodecim 1: 143–70.

66. Loukas M, Clarke P, Tubbs RS. (2007) Accessory breasts: A historical and current perspective. Am Surg 73(5): 525–528. 17521013

67. Veltmaat JM, Mailleux AA, Thiery JP, Bellusci S. (2003) Mouse embryonic mammogenesis as a model for the molecular regulation of pattern formation. Differentiation 71(1): 1–17. doi: 10.1046/j.1432-0436.2003.700601.x 12558599

68. Brambell F, Davis D, Jarvis J. (1941) Reproduction of the multimammate mouse (Mastomys erythroleucus temm.) of sierra leone. Proceedings of the Zoological Society of London B111(1–2): 1–11.

69. Colosimo PF, Hosemann KE, Balabhadra S, Villarreal G Jr, Dickson M, et al. (2005) Widespread parallel evolution in sticklebacks by repeated fixation of ectodysplasin alleles. Science 307(5717): 1928–1933. 307/5717/1928 [pii]. 15790847

70. Kamberov YG, Wang S, Tan J, Gerbault P, Wark A, et al. (2013) Modeling recent human evolution in mice by expression of a selected EDAR variant. Cell 152(4): 691–702. doi: 10.1016/j.cell.2013.01.016 23415220

71. Bhakar AL, Tannis LL, Zeindler C, Russo MP, Jobin C, et al. (2002) Constitutive nuclear factor-kappa B activity is required for central neuron survival. J Neurosci 22(19): 8466–8475. 12351721

72. Edlund RK, Ohyama T, Kantarci H, Riley BB, Groves AK. (2014) Foxi transcription factors promote pharyngeal arch development by regulating formation of FGF signaling centers. Dev Biol 390(1): 1–13. doi: 10.1016/j.ydbio.2014.03.004 24650709

73. Martin P. (1990) Tissue patterning in the developing mouse limb. Int J Dev Biol 34(3): 323–336. 1702679

74. Pispa J, Pummila M, Barker PA, Thesleff I, Mikkola ML. (2008) Edar and troy signalling pathways act redundantly to regulate initiation of hair follicle development. Hum Mol Genet 17(21): 3380–3391. doi: 10.1093/hmg/ddn232 18689798

75. Gaide O, Schneider P. (2003) Permanent correction of an inherited ectodermal dysplasia with recombinant EDA. Nat Med 9(5): 614–618. doi: 10.1038/nm861 12692542

76. Liu JG, Tabata MJ, Yamashita K, Matsumura T, Iwamoto M, et al. (1998) Developmental role of PTHrP in murine molars. Eur J Oral Sci 106 Suppl 1: 143–146. 9541217

77. Wang J, Shackleford GM. (1996) Murine Wnt10a and Wnt10b: Cloning and expression in developing limbs, face and skin of embryos and in adults. Oncogene 13(7): 1537–1544. 8875992

78. Dassule HR, McMahon AP. (1998) Analysis of epithelial-mesenchymal interactions in the initial morphogenesis of the mammalian tooth. Dev Biol 202(2): 215–227. S0012-1606(98)98992-8 [pii]. 9769173

79. Laurikkala J, Pispa J, Jung HS, Nieminen P, Mikkola M, et al. (2002) Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor edar. Development 129(10): 2541–2553. 11973284

80. Laurikkala J, Mikkola M, Mustonen T, Aberg T, Koppinen P, et al. (2001) TNF signaling via the ligand-receptor pair ectodysplasin and edar controls the function of epithelial signaling centers and is regulated by wnt and activin during tooth organogenesis. Dev Biol 229(2): 443–455. doi: 10.1006/dbio.2000.9955 11203701

81. Edgar R, Domrachev M, Lash AE. (2002) Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30(1): 207–210. 11752295