DOI: 10.1073/pnas.1836391100. <i>Drosophila spalt/spalt-related</i> mutants exhibit Townes-Brocks' syndrome phenotypes

Drosophila spalt/spalt-related mutants exhibit Townes-Brocks' syndrome phenotypes

10.1073/pnas.1836391100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Mutations in SALL1 , the human homolog of the Drosophila spalt gene, result in Townes-Brocks' syndrome, which is characterized by hand/foot, anogenital, renal, and ear anomalies, including sensorineural deafness. spalt genes encode zinc finger transcription factors that are found in animals as diverse as worms, insects, and vertebrates. Here, we examine the effect of losing both of the spalt genes, spalt and spalt-related , in the fruit fly Drosophila melanogaster , and report defects similar to those in humans with Townes-Brocks' syndrome. Loss of both spalt and spalt-related function in flies yields morphological defects in the testes, genitalia, and the antenna. Furthermore, spalt / spalt-related mutant antennae show severe reductions in Johnston's organ, the major auditory organ in Drosophila . Electrophysiological analyses confirm that spalt / spalt-related mutant flies are deaf. These commonalities suggest that there is functional conservation for spalt genes between vertebrates and insects.

Bibliography

Dong, P. D. S., Todi, S. V., Eberl, D. F., & Boekhoff-Falk, G. (2003). Drosophila spalt/spalt-related mutants exhibit Townes-Brocksâ syndrome phenotypes. Proceedings of the National Academy of Sciences, 100(18), 10293â10298.

Authors 4

P. D. Si Dong (first)
Sokol V. Todi (additional)
Daniel F. Eberl (additional)
Grace Boekhoff-Falk (additional)

References 57 Referenced 41

10.1038/ng0198-81
10.1006/geno.1996.0631
10.1006/geno.1999.6005
10.1086/302238
10.1002/(SICI)1098-1004(199911)14:5<377::AID-HUMU3>3.0.CO;2-A
10.1002/1098-1004(200012)16:6<460::AID-HUMU2>3.0.CO;2-4
10.1097/00125817-200107000-00007
10.1016/S0022-3476(72)80302-0
10.1016/S0022-3476(78)80518-6
10.1002/ajmg.1320180118
Powell, C. M. & Michaelis, R. C. (1999) J. Med. Genet. 36, 89-93.10051003 / J. Med. Genet. (1999)
10.1007/s004670050006
10.1002/1096-8628(20010815)102:3<250::AID-AJMG1479>3.0.CO;2-Q
Martinez-Frias, M. L., Bermejo Sanchez, E., Arroyo Carrera, I., Perez Fernandez, J. L., Pardo Romero, M., Buron Martinez, E. & Hernandez Ramon, F. (1999) Anal. Esp. Pediatr. 50, 57-60. / Anal. Esp. Pediatr. (1999)
Ferraz, F. G., Nunes, L., Ferraz, M. E., Sousa, J. P., Santos, M., Carvalho, C. & Maroteaux, P. (1989) Ann. Genet. 32, 120-123.2667456 / Ann. Genet. (1989)
10.1007/BF02072048
10.1007/s004670100624
10.1016/0925-4773(96)00516-3
10.1016/S0925-4773(01)00364-1
10.1002/j.1460-2075.1994.tb06246.x
10.1101/gad.10.15.1953
10.1016/0925-4773(95)00485-8
Koster, R., Stick, R., Loosli, F. & Wittbrodt, J. (1997) Mech. Dev. 124, 3147-3156. / Mech. Dev. (1997)
10.1006/bbrc.1999.1479
10.1159/000015598
10.1006/dbio.2000.9852
10.1007/s003350010012
10.1016/S0925-4773(01)00296-9
10.1038/381421a0
Kuhnlein, R. P. & Schuh, R. (1996) Development (Cambridge, U.K.) 122, 2215-2223. / Development (Cambridge, U.K.) (1996)
Sturtevant, M., Biehs, B., Marin, E. & Bier, E. (1997) Development (Cambridge, U.K.) 124, 21-32. / Development (Cambridge, U.K.) (1997)
de Celis, J. F., Barrio, R. & Kafatos, F. C. (1999) Development (Cambridge, U.K.) 126, 2653-2662. / Development (Cambridge, U.K.) (1999)
10.1016/S0092-8674(00)81114-9
Elstob, P. R., Brodu, V. & Gould, A. P. (2001) Development (Cambridge, U.K.) 128, 723-732. / Development (Cambridge, U.K.) (2001)
Rusten, T. E., Cantera, R., Urban, J., Technau, G., Kafatos, F. C. & Barrio, R. (2001) Development (Cambridge, U.K.) 128, 711-722. / Development (Cambridge, U.K.) (2001)
10.1038/35091076
10.1101/gad.5.12b.2467
Dong, P. D. S., Chu, J. & Panganiban, G. (2000) Development (Cambridge, U.K.) 127, 209-216. / Development (Cambridge, U.K.) (2000)
10.1006/dbio.1999.9434
10.1093/genetics/139.1.203
Xu, T. & Rubin, G. (1993) Development (Cambridge, U.K.) 117, 1223-1237. / Development (Cambridge, U.K.) (1993)
Newsome, T. P., Asling, B. & Dickson, B. J. (2000) Development (Cambridge, U.K.) 127, 851-860. / Development (Cambridge, U.K.) (2000)
Halder, G., Callaerts, P., Flister, S., Walldorf, U., Kloter, U. & Gehring, W. (1998) Development (Cambridge, U.K.) 125, 2181-2191. / Development (Cambridge, U.K.) (1998)
Stern D. L. & Sucena E. (2000) in Preparation of Larval and Adult Cuticles for Light Microscopy eds. Sullivan W. Ashburner M. & Hawley R. S. (Cold Spring Harbor Lab. Press Plainview NY) pp. 601-616.
Downs, K. M., Gifford, S., Blahnik, M. & Gardner, R. L. (1998) Development (Cambridge, U.K.) 125, 4507-4520. / Development (Cambridge, U.K.) (1998)
10.1523/JNEUROSCI.20-16-05981.2000
10.1177/01945998941113P103
10.1016/S0959-4388(99)80058-0
10.1038/35082144
Dong, P. D. S., Dicks, J. S. & Panganiban, G. (2002) Development (Cambridge, U.K.) 129, 1967-1974. / Development (Cambridge, U.K.) (2002)
Jarman, A. P., Sun, Y., Jan, L. Y. & Jan, Y. N. (1995) Development (Cambridge, U.K.) 121, 2019-2030. / Development (Cambridge, U.K.) (1995)
10.1136/jmg.37.4.303
Nishinakamura, R., Matsumoto, Y., Nakao, K., Nakamura, K., Sato, A., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Scully, S., Lacey, D. L., et al. (2001) Development (Cambridge, U.K.) 128, 3105-3115. / Development (Cambridge, U.K.) (2001)
10.1093/hmg/5.5.571
10.1093/hmg/3.8.1345
10.1101/gad.988402
10.1126/science.284.5421.1837

Dates

Type	When
Created	22 years ago (Sept. 2, 2003, 1:27 p.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5:23 a.m.)
Indexed	3 months, 4 weeks ago (May 3, 2025, 10:29 p.m.)
Issued	22 years ago (Aug. 18, 2003)
Published	22 years ago (Aug. 18, 2003)
Published Online	22 years ago (Aug. 18, 2003)
Published Print	22 years ago (Sept. 2, 2003)

Funders 0

None

BibTeX

@article{Dong_2003, title={Drosophila spalt/spalt-related mutants exhibit Townes-Brocks’ syndrome phenotypes}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1836391100}, DOI={10.1073/pnas.1836391100}, number={18}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Dong, P. D. Si and Todi, Sokol V. and Eberl, Daniel F. and Boekhoff-Falk, Grace}, year={2003}, month=aug, pages={10293–10298} }

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