The secreted product of Xenopus gene lunatic fringe, a vertebrate signaling molecule

Science

Volumn 273, Issue 5273, 1996, Pages 355-358

  Wu, Jane Y ^a   Wen, Leng ^a   Zhang, Wan Jiang ^a   Rao, Yi ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA;

ARTICLE; GENETIC ANALYSIS; PATTERN RECOGNITION; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN SECRETION; VERTEBRATE; XENOPUS;

EID: 0029895311     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.273.5273.355     Document Type: Article

References (46)

1. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
2. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
3. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
4. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
5. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
6. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
7. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
8. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
9. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
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11. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
12. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
13. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
14. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
15. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
16. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
17. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
18. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
19. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
20. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
21. P. S. Klein and D. A. Melton, Endocrinol. Rev. 15, 326 (1994); I. B. Dawid and M. Taira, Bioessays 16, 385 (1994); J. M. Slack, Curr. Biol. 4, 116 (1994); C. M. Jones and J. C. Smith, ibid. 5, 574 (1995); J. M. W. Slack, B. G. Darlington, J. K. Heath, S. F. Godsave, Nature 326, 197 (1987); J. C. Smith, Development 99, 3 (1987); D. L. Weeks and D. A. Melton, Cell 51, 861 (1987); D. Kimelman and M. Kirschner, ibid., p. 869; F. M. Rosa et al., Science 239, 783 (1988); J. M. W. Slack, B. G. Darlington, L. L. Gillespie, S. F. Godsave, G. D. Paterno, Development 107, 141 (1989); M. Asashima et al., Roux's Arch. Dev. Biol. 198, 330 (1990); J. C. Smith, B. M. J. Price, K. Van Nimmen, D. Huylebroeck, Nature 345, 729 (1990); S. Sokol, G. G. Wong, D. A. Melton. Science 249, 561 (1990); G. Thomsen et al., Cell 63, 485 (1990); J. B. A. Green and J. C. Smith, Nature 347, 391 (1990); J. B. A. Green, H. V. New, J. C. Smith, Cell 71, 731 (1992); A. J. M. van den Eijnden-Van Raaij et al., Nature 345, 732 (1990); C. M. Jones, M. R. Kuehn, B. L. M. Hogan, J. C. Smith, C. V. E. Wright, Development 121, 3651 (1995); M. Koster et al., Mech. Dev. 33, 191 (1991); L. Dale, G. Howes, B. M. J. Price, J. C. Smith, Development 115, 573 (1992); C. M. Jones, K. M. Lyons, P. M. Lapan, C. V. E. Wright, B. J. M. Hogan, ibid., p. 639.
22. E. Amaya, T. J. Musci, M. W. Kirschner, Cell 66, 257 (1991); R. Cornell and D. Kimelman, Development 120, 453 (1994); C. LaBonne and M. Whitman, ibid., p. 463.
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27. A. Hemmati-Brivanlou and D. A. Melton, Nature 359, 609 (1992); D. S. Kessler and D. A. Melton, Science 266, 596 (1994); S. Schulte-Merker, J. C. Smith, L. Dale, EMBO J. 13, 3533 (1994).
28. A. Hemmati-Brivanlou and D. A. Melton, Nature 359, 609 (1992); D. S. Kessler and D. A. Melton, Science 266, 596 (1994); S. Schulte-Merker, J. C. Smith, L. Dale, EMBO J. 13, 3533 (1994).
29. A. Hemmati-Brivanlou and D. A. Melton, Nature 359, 609 (1992); D. S. Kessler and D. A. Melton, Science 266, 596 (1994); S. Schulte-Merker, J. C. Smith, L. Dale, EMBO J. 13, 3533 (1994).
30. A. Vassalli, M. M. Matzuk, H. A. Gardner, K. F. Lee, R. Jaenisch, Genes Dev. 8, 414 (1994); M. M. Matzuk et al., Nature 374, 354 (1995); M. M. Matzuk, T. R. Kumar, A. Bradley, ibid., p. 356.
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33. K. D. Irvine and E. Wieschaus, Cell 79, 595 (1994).
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36. J. Kim, K. D. Irvine, S. B. Carroll, ibid. 82, 795 (1995); G. Campbell, T. Weaver, A. Tomlinson, ibid. 74, 1113 (1993); T. Tabata and T. B. Kornberg, ibid. 76, 89 (1994).
37. Several pairs of degenerate PCR primers for fringe were designed and the following pair worked: the upstream sequence CGI YTI TGY TGY AAR ATG coding for ALCCKM, and the downstream sequence CAR AAI CCI GCI CCI CCI GT coding for GGAGFC (16). Complementary DNAs (cDNAs) from stages 10.5, 13, and 28 Xenopus embryos were used as templates. The PCR conditions were as follows: 94°C for 3 min, 53°C for 1 min, and 72°C for 2 min for 1 cycle, followed by 36 cycles of 94°C for 45 s, 53°C for 1 min, and 72°C for 2 min. A band of about 280 base pairs was obtained and subcloned into pBluescript SK. About 100 colonies were obtained, and 24 individual cDNAs have been isolated. Nine of these clones were sequenced and found to encode two distinct Xenopus Fng proteins: five clones encoding lFng and four clones encoding rFng. The fragments were used as probes to screen stage 17 and stage 28 Xenopus embryonic cDNA libraries. Positive clones were isolated (10 for lFng and 7 for rFng), and the longest cDNAs (1.4 kb for lFng and 2.5 kb for rFng) were sequenced. Both of the sequences contained stop codons in all three frames upstream of the first AUG. The longest open reading frames encoded full-length proteins for lFng and rFng. In the case of rFng, the amino acid sequence shown in Fig. 1, B and D, is likely to be the product of an alternatively spliced form. At the COOH-terminus of the sequence shown, a stop codon is introduced by a sequence of 67 nucleotides that fits the consensus of an intron. If this intron is spliced out, a sequence encoding FKSVHCLLYSDTDWCPNHKHNPTT (16) will be added to the COOH-terminus. Low-stringency hybridization was carried out with 30% formamide, 8× standard saline citrate (SSC), 5×Denhardt's solution, 0.5% SDS, and salmon sperm DNA (100 μg/ml). Fifteen positive plaques were isolated for further screening, and a single plaque went through secondary screening. A cDNA of 2.3 kb was isolated after tertiary screening. It was sequenced and found to encode rFng. In the 3′ end of the coding region, this cDNA also contains the intron described above so that it predicts the same product as shown in Fig. 1B.
38. 35S-labeled methionine with a coupled transcription-translation rabbit reticulocyte lysate system (Promega). To examine glycosylation and signal peptide cleavage, we used a canine pancreatic microsomal membrane preparation (Promega) at a concentration of 2 μl of microsomal membrane preparation in a 25-μl reaction. β-Lactamase was used as a positive control for signal peptide cleavage by the microsomal membrane preparation. To confirm that the appearance of higher molecular weight bands was the result of glycosylation, we used the peptide N-glycosidase F (PNGase F) (New England Biolabs, Beverly, MA). PNGase F cleaves between the innermost N-acetylglucosamine and asparagine residues from N-linked glycoproteins. PNGase F was added to the in vitro translation products after the proteins were denatured and incubated for 3 hours at 37°C. The products were analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) followed by autoradiography.
39. To analyze the expression of lFng protein in mammalian cells, we cultured COS-7 cells in Dulbecco's modified essential medium (DMEM) (Gibco-BRL) supplemented with 5% fetal bovine serum (Hyclone, Logan, UT) and grown to 50% confluence in 100-mm dishes. Next, 20 μg of FrgpcDNA, FrgHispcDNA, or control vector was transfected into COS-7 cells with 25 μg of Lipofectin (Gibco-BRL), Twenty-four hours after transfection, the medium was removed and fresh medium was added. The cells were further cultured for 96 hours, and conditioned media were collected and stored in small samples at -70°C. For detection of the protein secreted by transfected COS-7 cells, nickel agarose was used to purify the His-tagged lFng protein from 10 ml of conditioned medium of FrgHispcDNA-transfected cells. His-tagged lFng protein from a 5-ml equivalent of the conditioned medium was analyzed on SDS-PAGE, transferred to a nitrocellulose filter, and detected by a T7 antibody that recognized the T7 epitope present in the fusion protein. The concentration of lFng protein was estimated by comparison with a T7-tagged recombinant protein of known concentration.
40. Whole-mount in situ hybridization was performed essentially as described [R. M. Harland, in Methods in Cell Biology, B. K. Kay and H. B. Peng, Eds. (Academic Press, San Diego, CA, 1991), vol. 36, pp. 685-695].
41. L. Wen and Y. Rao, data not shown.
42. Animal cap assays were previously described (15). Blastula animal cap explants were isolated and treated for 1 hour with lFng-containing medium or purified His-tagged lFng protein. His-tagged lFng was purified with nickel agarose (Qiagen) from conditioned medium from COS cells transfected with pcDNAIII expressing His-tagged lFng. Nickel agarose was equilibrated in DMEM and then incubated with either lFng-conditioned medium or control medium (from COS cells transfected with the vector plasmid) at 4°C for 3 hours. After binding, the beads were washed three times with DMEM and resuspended in 0.5× MMR (modified Ringer's) solution containing bovine serum albumin (100 μg/ ml). Pictures of animal caps were taken at stage 13 for overall morphology. Some caps were fixed at stage 23 and hybridized in situ with a muscle-specific actin probe. Other caps were fixed at stage 35 for examination of histology. Sections (8 μm thick) were made from paraffin-embedded animal caps.
43. Sequences of most of the PCR primers have been described in (15). Additional primers are as follows: Xwnt-8 (upstream: AGA TGA CGG CAT TCC AGA; downstream: TCT CCC GAT ATC TCA GGA), noggin (upstream: TGC TGA GAC TCT TGG ACT; downstream: AAT GCT TCG CCA AGC GAA), globin (upstream: GCC TAC AAC CTG AGA GTG G; downstream: CAG GCT GGT GAG CTG CCC), and lFng (upstream: GAG AGC AAT ATG CGT CCT G; downstream: GTA AGC AGC TTT CCA CGG) (DNAgency).
44. Y. Rao, Genes Dev. 8, 939 (1994).
45. Abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, lie; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
46. We would like to thank K. Irvine and E. Wieschaus for providing us with the Drosophila fng probe; C. Tabin, E. Laufer, S. Sokol, Y. Wang, R. Johnson, and T. Vogt for sharing information and nomenclature of the vertebrate fng genes; and R. Cagan, J. Gordon, R. Kopan, M. Nonet, D. Omitz, J. Sanes, and A. Strauss for helpful comments on the manuscript.