Genes in Enteric Nervous System Development

Genes Known to be Important For ENS Development

A more extensive annotated list is in our review.

Gene Name Molecular Function Reference
  ENS Phenotype

Ret Tyrosine kinase receptor (1)
  extensive aganglionosis
GFRα1 Ret co-receptor (2,3)
  extensive aganglionosis
GDNF Ret ligand (4-6)
  extensive aganglionosis
GFRα2 Ret co-receptor (7)
  reduced neuronal fibers
Neurturin Ret ligand (8)
  reduced neuronal fibers
Artemin Ret ligand (9)
  reduced sympathetic innervation
Trk C Tyrosine kinase receptor (10)
  hypoganglionosis
NT-3 Trk C ligand (10)
  hypoganglionosis
Sox 10 Transcription factor (11,12)
  extensive aganglionosis
Mash 1 Transcription factor (13,14)
  selective neuronal loss
Hoxa-4 Transcription factor (15)
  hypoganglionosis (if over-expressed)
Hox11L1 Transcription factor (16)
  hyperganglionosis
Pax3 Transcription factor (17)
  aganglionosis
ENRB Receptor (18,19)
  distal aganglionosis
Endothelin-3 ENRB ligand (20)
  distal aganglionosis
ECE-1 Endothelin processing (21)
  distal aganglionosis
Sonic hedgehog Morphogen (22)
  ectopic enteric neurons
Indian hedgehog Morphogen (22)
  aganglionosis
SIP1 Signal Transduction (23,24)
  aganglionosis

 

References

 

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  2. Cacalano, G., Farinas, I., Wang, L.-C., Hagler, K., Forgie, A., Moore, M., Armanini, M., Phillips, H., Ryan, A. M., Reichardt, L. F., Hynes, M., Davies, A., and Rosenthal, A. (1998) Neuron 21, 53-62

  3. Enomoto, H., Araki, T., Jackman, A., Heuckeroth, R. O., Snider, W. D., Johnson, E. M. J., and Milbrandt, J. (1998) Neuron 21, 317-324

  4. Moore, M. W., Klein, R. D., Farinas, I., Sauer, H., Armanini, M., Phillips, H., Reichart, L. F., Ryan, A. M., Carver-Moore, K., and Rosenthal, A. (1996) Nature 382, 76-79

  5. Pichel, J. G., Shen, L., Hui, S. Z., Granholm, A.-C., Drago, J., Grinberg, A., Lee, E. J., Huang, S. P., Saarma, M., Hoffer, B. J., Sariola, H., and Westphal, H. (1996) Nature 382, 73-76

  6. Sanchez, M. P., Silos-Santiago, I., Frisen, J., He, B., Lira, S. A., and Barbacid, M. (1996) Nature 382, 70-73

  7. Rossi, J., Luukko, K., Poteryaev, D., Laurikainen, A., Sun, Y. F., Laakso, T., Eerikainen, S., Tuominen, R., Lakso, M., Rauvala, H., Arumae, U., Pasternack, M., Saarma, M., and Airaksinen, M. S. (1998) Neuron 22, 243-252

  8. Heuckeroth, R. O., Enomoto, H., Grider, J. R., Golden, J. P., Hanke, J. A., Jackman, A., Molliver, D. C., Bardgett, M. E., Snider, W. D., Johnson, E. M., Jr., and Milbrandt, J. (1999) Neuron 22, 253-263

  9. Honma Y., Araki T., Gianino S., Bruce A., Heuckeroth R., Johnson E., Milbrandt, J. (2002) Neuron 35(2): 267-82.

  10. Chalazonitis, A., Pham, T. D., Rothman, T. P., DiStefano, P. S., Bothwell, M., Blair-Flynn, J., Tessarollo, L., and Gershon, M. D. (2001) J Neurosci 21, 5620-5636

  11. Pingault, V., Bondurand, N., Kuhlbrodt, K., Goerich, D. E., Prehu, M.-O., Puliti, A., Herbarth, B., Hermans-Borgmeyer, I., Legius, E., Matthijs, G., Amiel, J., Lyonnet, S., Ceccherini, I., Romeo, G., Smith, J. C., Read, A. P., Wegner, M., and Goossens, M. (1998) Nature Genetics 18, 171-173

  12. Southard-Smith, E. M., Kos, L., and Pavan, W. J. (1998) Nature Genetics 18, 60-64

  13. Sang, Q., Ciampoli, D., Greferath, U., Sommer, L., and Young, H. M. (1999) J. Comparative Neurology 408, 1-10

  14. Blaugrund, E., Pham, T. D., Tennyson, V. M., Lo, L., Sommer, L., Anderson, D. J., and Gershon, M. D. (1996) Development 122, 309-320

  15. Wolgemuth, D. J., Behringer, R. R., Mostoller, M. P., Brinster, R. L., and Palmiter, R. D. (1989) Nature 337, 464-467

  16. Hatano, M., Aoki, D., Dezawa, M., Yusa, S., Iitsuka, Y., Koseki, H., Taniguchi, M., and Tokuhisa, T. (1997) J. Clin. Invest. 100, 795-801

  17. Lang, D., Chen, F., Milewski, R., Li, J., Lu, M. M., and Epstein, J. A. (2000) J. Clinical Investigation 106, 963-971

  18. Hosoda, K., Hammer, R. E., Richardson, J. A., Baynash, A. G., Cheung, J. C., Giaid, A., and Yanagisawa, M. (1994) Cell 79, 1267-1276

  19. Puffenberger, I. G., Hosoda, K., Washington, S. S., Nakao, K., deWit, D., Yanagisawa, M., and Chakravarti, A. (1994) Cell 79, 1257-1266

  20. Baynash, A. G., Hosoda, K., Giaid, A., Richardson, J. A., Emoto, N., Hammer, R. E., and Yanagisawa, M. (1994) Cell 79, 1277-1285

  21. Hofstra, R. M., Valdenaire, O., Arch, E., Osinga, J., Kroes, H., Loffler, B. M., Hamosh, A., Meijers, C., and Buys, C. H. (1999) Am J Hum Genet 64, 304-308

  22. Ramalho-Santos, M., Melton, D. A., and McMahon, A. P. (2000) Development 127, 2763-2772

  23. Wakamatsu, N., Yamada, Y., Yamada, K., Ono, T., Nomura, N., Taniguchi, H., Kitoh, H., Mutoh, N., Yamanaka, T., Mushiake, K., Kato, K., Sonta, S., and Nagaya, M. (2001) Nat Genet 27, 369-370

  24. Yamada, K., Yamada, Y., Nomura, N., Miura, K., Wakako, R., Hayakawa, C., Matsumoto, A., Kumagai, T., Yoshimura, I., Miyazaki, S., Kato, K., Sonta, S., Ono, H., Yamanaka, T., Nagaya, M., and Wakamatsu, N. (2001) Am J Hum Genet 69, 1178-1185