Genes in ENS Development  

Genes Known to be Important For ENS Development

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Artemin	Ret ligand	(unpublished, ROH)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

References

1. Schuchardt, A., D'Agati, V., Larsson-Blomberg, L., Constantini, F., and Pachnis, V. (1994) Nature 367, 380-383

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. 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

10. 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

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

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

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

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

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

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

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

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

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

20. 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

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

22. 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

23. 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