Loss of connexin43-mediated gap junctional coupling in the mesenchyme of limb buds leads to altered expression of morphogens in mice

Human Molecular Genetics

Volumn 18, Issue 15, 2009, Pages 2899-2911

  Dobrowolski, Radoslaw ^a,d   Hertig, Gerda ^a   Lechner, Hildegard ^b   Wörsdörfer, Philipp ^a   Wulf, Volker ^a   Dicke, Nikolai ^a   Eckert, Dawid ^b   Bauer, Reinhard ^b   Schorle, Hubert ^b   Willecke, Klaus ^a,c  

^a Institute of Human Genetics   (Germany)

^b UNIVERSITY OF BONN   (Germany)

^c University of Bonn ^*  (Germany)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN 2; CONNEXIN 43; FIBROBLAST GROWTH FACTOR 4; FIBROBLAST GROWTH FACTOR 8; SONIC HEDGEHOG PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CONTROLLED STUDY; EMBRYO; FEEDBACK SYSTEM; GAP JUNCTION; GENE EXPRESSION; GENE EXPRESSION REGULATION; LIMB BUD; LIMB DEVELOPMENT; MESENCHYME; MOUSE; NONHUMAN; OCULODENTODIGITAL SYNDROME; POINT MUTATION; PRIORITY JOURNAL; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; SYNDACTYLY; UPREGULATION;

ANIMALS; BONE MORPHOGENETIC PROTEIN 2; CONNEXIN 43; DISEASE MODELS, ANIMAL; FEMALE; FIBROBLAST GROWTH FACTORS; GAP JUNCTIONS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HEDGEHOG PROTEINS; HUMANS; LIMB BUDS; MALE; MESODERM; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; SYNDACTYLY;

ERINACEIDAE; MUS;

EID: 67650751755     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddp227     Document Type: Article

References (50)

1. Schneider, R.A., Hu, D. and Helms, J.A. (1999) From head to toe: conservation of molecular signals regulating limb and craniofacial morphogenesis. Cell Tissue Res., 296, 103-109.
2. Riddle, R.D., Johnson, R.L., Laufer, E. and Tabin, C. (1993) Sonic hedgehog mediates the polarizing activity of the ZPA. Cell, 75 1401-1416.
3. Laufer, E., Nelson, C.E., Johnson, R.L., Morgan, B.A. and Tabin, C. (1994) Sonic hedgehog and Fgf-4 act through a signaling cascade and feedback loop to integrate growth and patterning of the developing limb bud. Cell, 79, 993-1003.
4. Niswander, L., Jeffrey, S., Martin, G.R. and Tickle, C. (1994) A positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature, 371, 609-612.
5. Scherz, P.J., Harfe, B.D., McMahon, A.P. and Tabin, C.J. (2004) The limb bud Shh-Fgf feedback loop is terminated by expansion of former ZPA cells. Science, 305, 396-399.
6. Capdevila, J. and Johnson, R.L. (1998) Endogenous and ectopic expression of noggin suggests a conserved mechanism for regulation of BMP function during limb and somite patterning. Dev. Biol., 197, 205-217.
7. Pajni-Underwood, S., Wilson, C.P., Elder, C., Mishina, Y. and Lewandoski, M. (2007) BMP signals control limb bud interdigital programmed cell death by regulating Fgf signaling. Development, 12, 2359-2368.
8. Flenniken, A.M., Osborne, L.R., Anderson, N., Ciliberti, N., Fleming, C., Gittens, J.E., Gong, X.Q., Kelsey, L.B., Lounsbury, C., Moreno, L. et al. (2005) A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia. Development, 132, 4375-4386.
9. Dobrowolski, R., Sasse, P., Schrickel, J.W., Watkins, M., Kim, J.S., Rackauskas, M., Troatz, C., Ghanem, A., Tiemann, K., Degen, J. et al. (2008) The conditional connexin43G138R mouse mutant represents a new model of hereditary oculodentodigital dysplasia in humans. Hum. Mol. Genet., 4, 539-554.
10. Kalcheva, N., Qu, J., Sandeep, N., Garcia, L., Zhang, J., Wang, Z., Lampe, P.D., Suadicani, S.O., Spray, D.C. and Fishman, G.I. (2007) Gap junction remodeling and cardiac arrhythmogenesis in a murine model of oculodentodigital dysplasia. Proc. Natl. Acad. Sci. USA, 104 20512-20516.
11. Söhl, G. and Willecke, K. (2003) An update on connexin genes and their nomenclature in mouse and man. Cell. Commun. Adhes., 10 173-180.
12. Bennett, M.V.L. and Verselis, V.K. (1992) Biophysics of gap junctions. Semin. Cell. Biol., 3, 29-47.
13. Bruzzone, S., Guida, L., Zocchi, E., Franco, L. and De Flora, A. (2001) Connexin 43 hemi channels mediate Ca2+-regulated transmembrane NAD+ fluxes in intact cells. FASEB J., 15, 10-12.
14. Makarenkova, H. and Patel, K. (1999) Gap junction signaling mediated through connexin-43 is required for chick limb development. Dev. Biol., 2, 380-392.
15. Law, L.Y., Lin, J.S., Becker, D.L. and Green, C.R. (2002) Knockdown of connexin43-mediated regulation of the zone of polarizing activity in the developing chick limb leads to digit truncation. Dev. Growth Differ. 6, 537-547.
16. Zhang, W., Green, C. and Stott, N.S. (2002) Bone morphogenetic protein-2 modulation of chondrogenic differentiation in vitro involves gap junction-mediated intercellular communication. J. Cell. Physiol., 193, 233-243.
17. Theis, M., Magin, T.M., Plum, A. and Willecke, K. (2000) General or cell type-specific deletion and replacement of connexin-coding DNA in the mouse. Methods, 20, 205-218.
18. Byrne, C., Tainsky, M. and Fuchs, E. (1994) Programming gene expression in developing epidermis. Development, 120, 2369-2383.
19. Logan, M., Martin, J.F., Nagy, A., Lobe, C., Olson, E.N. et al. (2002) Expression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis, 33, 77-80.
20. Laird, D.W., Yancey, S.B., Bugga, L. and Revel, J.P. (1992) Connexin expression and gap junction communication compartments in the developing mouse limb. Dev. Dyn., 195, 153-161.
21. Zou, H. and Niswander, L. (1996) Requirement for BMP signaling in interdigital apoptosis and scale formation. Science, 272, 738-741.
22. Reddi, A.H. and Huggins, C. (1972) Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. Proc. Natl. Acad. Sci. USA, 69, 1601-1605.
23. Urist, M.R. (1965) Bone: Formation by autoinduction. Science, 150, 893-899.
24. Wozney, J.M., Rosen, V., Celeste, A.J., Mitsock, L.M., Whitters, M.J. et al. (1988) Novel regulators of bone formation: Molecular clones and activities. Science, 242, 1528-1534.
25. Francis, P.H., Richardson, M.K., Brickell, P.M. and Tickle, C. (1994) Bone morphogenetic proteins and a signaling pathway that controls patterning in the developing chick limb. Development, 120, 209-218.
26. Yang, Y., Drossopoulou, G., Chuang, P.T., Duprez, D., Marti, E. et al. (1997) Relationship between dose, distance and time in Sonic Hedgehog-mediated regulation of anteroposterior polarity in the chick limb. Development, 124, 4393-4404.
27. Bandyopadhyay, A., Tsuji, K., Cox, K., Harfe, B.D., Rosen, V. and Tabin, C.J. (2006) Genetic analysis of the roles of BMP2, BMP4 and BMP7 in limb patterning and skeletogenesis. PLoS Genet., 2, e216.
28. Chiang, C., Litingtung, Y., Lee, E., Young, K.E., Corden, J.L. et al (1996) Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature, 383, 407-413.
29. Ganan, Y., Macias, D., Duterque-Coquillaud, M., Ros, M.A. and Hurle, J.M. (1996) Role of TGF beta s and BMPs as signals controlling the position of the digits and the areas of interdigital cell death in the developing chick limb autopod. Development, 122, 2349-2357.
30. Yokouchi, Y., Vogan, K.J., Pearse, R.V. II and Tabin, C.J. (1999) Antagonistic signaling by Caronte, a novel Cerberus-related gene, establishes left-right asymmetric gene expression. Cell, 98, 573-583.
31. Winnier, G., Blessing, M., Labosky, P.A. and Hogan, B.L. (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev., 9, 2105-2116.
32. Zhang, H. and Bradley, A. (1996) Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development, 122, 2977-2986.
33. Lai, A., Le, D.-N., Paznekas, W.A., Gifford, W.S., Wang Jabs, E. and Charles, A.C. (2006) Oculodentodigital dysplasia connexin43 mutations result in non-functional connexin hemichannels and gap junctions in C6 glioma cells. J. Cell. Sci., 119, 532-541.
34. Feistel, K. and Blum, M. (2008) Gap junctions relay Fgf8-mediated right-sided repression of Nodal in rabbit. Dev. Dyn., 237, 3516-3527.
35. Sáez, J.C., Connor, J.A., Spray, D.C. and Bennett, M.V. (1989) Hepatocyte gap junctions are permeable to the second messenger, inositol 1,4,5-trisphosphate, and to calcium ions. Proc. Natl. Acad. Sci. USA 8, 2708-2712.
36. Thies, R.S., Bauduy, M., Ashton, B.A., Kurtzberg, L., Wozney, J.M. and Rosen, V. (1992) Recombinant human bone morphogenetic protein-2 induces osteoblastic differentiation in W-20-17 stromal cells. Endocrinology 3, 1318-1324.
37. Nagase, T., Nagase, M., Osumi, N., Fukuda, S., Nakamura, S., Ohsaki, K., Harii, K., Asato, H. and Yoshimura, K. (2005) Craniofacial anomalies of the cultured mouse embryo induced by inhibition of sonic hedgehog signaling: An animal model of holoprosencephaly. J. Craniofac. Surg. 16, 80-88.
38. Roessler, E., Belloni, E., Gaudenz, K., Jay, P., Berta, P., Scherer, S.W., Tsui, L.C. and Muenke, M. (1996) Mutations in the human Sonic Hedgehog gene cause holoprosencephaly. Nat. Genet., 3, 357-360.
39. Cohen, M.M. Jr (1989) Perspectives on holoprosencephaly, Part I. Epidemiology, genetics, and syndromology. Teratology, 40, 211-235.
40. Cohen, M.M. Jr and Sulik, K.K. (1992) Perspectives on holoprosencephaly. Part II. Central nervous system, craniofacial anatomy, syndrome commentary, diagnostic approach, and experimental studies. J. Craniofac. Genet. Dev. Biol., 12, 196-244.
41. Fernandes, M., Gutin, G., Alcorn, H., McConnell, S.K. and Hébert, J.M. (2007) Mutations in the BMP pathway in mice support the existence of two molecular classes of holoprosencephaly. Development, 134 3789-3794.
42. Aberg, T., Wozney, J. and Thesleff, I. (1997) Expression patterns of bone morphogenetic proteins (Bmps) in the developing mouse tooth suggest roles in morphogenesis and cell differentiation. Dev. Dyn., 4 383-396.
43. Zhao, X., Zhang, Z., Song, Y., Zhang, X., Zhang, Y., Hu, Y., Fromm, S.H. and Chen, Y. (2000) Transgenically ectopic expression of Bmp4 to the Msx1 mutant dental mesenchyme restores downstream gene expression but represses Shh and Bmp2 in the enamel knot of wild type tooth germ. Mech. Dev., 1-2, 29-38.
44. Grieshammer, U., Cebrián, C., Ilagan, R., Meyers, E., Herzlinger, D. and Martin, G.R. (2005) Fgf8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons. Development, 132, 3847-3857.
45. Dent, J.A., Polson, A.G. and Klymkowsky, M.W. (1989) A whole-mount immunocytochemical analysis of the expression of the intermediate filament protein vimentin in Xenopus. Development, 1, 61-74.
46. LeMotte, P.K., Kuroiwa, A., Fessler, L.I. and Gehring, W.J. (1989) The homeotic gene Sex Combs Reduced of Drosophila: Gene structure and embryonic expression. EMBO J., 1, 219-227.
47. Traub, O., Eckert, R., Lichtenberg-Frate, H., Elfgang, C., Bastide, B., Scheidtmann, K.H., Hulser, D.F. and Willecke, K. (1994) Immunochemical and electrophysiological characterization of murine connexin 40 and -43 in mouse tissues and transfected human cells. Eur. J. Cell. Biol., 64, 101-112.
48. Pfisterer, P.J., Ehlermann, M., Hegen, M. and Schorle, H. (2002) A substractive gene expression screen suggests a role of transcription factor AP-2 alpha in control of proliferation and differentiation. J. Biol. Chem., 277, 6637-6644.
49. Feng, J., Sun, Q., Gao, C., Dong, J., Wei, X., Xing, H. and Li, H. (2007) Gene expression analysis of pancreatic cystic neoplasm in SV40Tag transgenic mice model. World J. Gastroenterol., 13, 2218-2222.
50. Herr, C., Smyth, N., Ullrich, S., Yun, F., Sasse, P., Hescheler, J., Fleischmann, B., Lasek, K., Brixius, K., Schwinger, R.H. et al. (2001) Loss of annexin A7 leads to alterations in frequency-induced shortening of isolated murine cardiomyocytes. Mol. Cell. Biol., 21, 4119-4128.