Abstract
T-box genes form a large family of conserved transcription factors with diverse roles in animal development, but so far functions for only a few have been studied in detail. Here we show that four Caenorhabditis elegansT-box genes and the even-skipped-like homeobox gene vab-7function within a regulatory network to control embryonic patterning and morphogenesis. tbx-8 and tbx-9 have functionally redundant roles in the intercalation of posterior dorsal hypodermal cells, in muscle cell positioning and in intestinal development. Inhibiting tbx-9alone using RNA interference (RNAi) produces worms that have a thickened,`bobbed tail' phenotype, similar to that seen in mutants of vab-7,which itself has been shown to pattern posterior muscle and hypodermal cells. In support of the view that these genes function in the same pathway, we find that tbx-8 and tbx-9 are both necessary and sufficient for vab-7 expression. In addition, a third T-box gene, tbx-30,acts to repress vab-7 expression in the anterior of embryos. We further show that vab-7 itself represses the T-box gene mab-9 in posterior cells. Thus, during posterior patterning in C. elegans, there are multiple interactions between T-box genes and the vab-7 homeobox gene. Evolutionary parallels in other organisms suggest that regulatory interactions between T-box genes and even-skipped homologues are conserved.
References
45
Referenced
37
-
Ahringer, J. (1996). Posterior patterning by the Caenorhabditis elegans even-skipped homolog vab-7. Genes Dev.10,1120-1130.
(
10.1101/gad.10.9.1120
) -
Ahringer, J. (1997). Maternal control of a zygotic patterning gene in Caenorhabditis elegans. Development124,3865-3869.
(
10.1242/dev.124.19.3865
) -
Bamshad, M., Le, T., Watkins, W. S., Dixon, M. E., Kramer, B. E., Roeder, A. D., Carey, J. C., Root, S., Schinzel, A., Van Maldergem, L. et al. (1999). The spectrum of mutations in TBX3:genotype/phenotype relationship in ulnar-mammary syndrome. Am. J. Hum. Genet.64,1550-1562.
(
10.1086/302417
) -
Basson, C. T., Huang, T., Lin, R. C., Bachinsky, D. R.,Weremowicz, S., Vaglio, A., Bruzzone, R., Quadrelli, R., Lerone, M., Romeo, G. et al. (1999). Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. Proc. Natl. Acad. Sci. USA96,2919-2924.
(
10.1073/pnas.96.6.2919
) -
Braybrook, C., Doudney, K., Marcano, A. C., Arnason, A.,Bjornsson, A., Patton, M. A., Goodfellow, P. J., Moore, G. E. and Stanier,P. (2001). The T-box transcription factor gene TBX22is mutated in X-linked cleft palate and ankyloglossia. Nat. Genet.29,179-183.
(
10.1038/ng730
) -
Brown, S. J., Parrish, J. K., Beeman, R. W. and Denell, R. E. (1997). Molecular characterization and embryonic expression of the even-skipped ortholog of Tribolium castaneum. Mech. Dev.61,165-173.
(
10.1016/S0925-4773(96)00642-9
) -
Chapman, D. L. and Papaioannou, V. E. (1998). Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6. Nature391,695-697.
(
10.1038/35624
) -
Chin-Sang, I. D. and Chisholm, A. D. (2000). Form of the worm: genetics of epidermal morphogenesis in C. elegans. Trends Genet.16,544-551.
(
10.1016/S0168-9525(00)02143-0
) -
Conlon, F. L. and Smith, J. C. (1999). Interference with brachyury function inhibits convergent extension,causes apoptosis, and reveals separate requirements in the FGF and activin signalling pathways. Dev. Biol.213,85-100.
(
10.1006/dbio.1999.9330
) -
Conlon, F. L., Sedgwick, S. G., Weston, K. M. and Smith, J. C. (1996). Inhibition of Xbra transcription activation causes defects in mesodermal patterning and reveals autoregulation of Xbra in dorsal mesoderm. Development122,2427-2435.
(
10.1242/dev.122.8.2427
) -
Cunliffe, V. and Smith, J. C. (1992). Ectopic mesoderm formation in Xenopus embryos caused by widespread expression of a Brachyury homologue. Nature358,427-430.
(
10.1038/358427a0
) - Esmaeili, B., Ross, J., Neades, C., Miller, D. M. III and Ahringer, J. (2002). The C. elegans even-skippedhomologue, vab-7, specifies DB motoneurone identity and axon trajectory. Development129,853-862.
-
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E. and Mello, C. C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature391,806-811.
(
10.1038/35888
) - Goh, P.-Y. and Bogaert, T. (1991). Positioning and maintenance of embryonic body wall muscle attachments in C. elegans requires the mup-1 gene. Development111,667-681.
-
Griffin, K. J., Amacher, S. L., Kimmel, C. B. and Kimelman,D. (1998). Molecular identification of spadetail: regulation of zebrafish trunk and tail mesoderm formation by T-box genes. Development125,3379-3388.
(
10.1242/dev.125.17.3379
) -
Han, K. and Manley, J. L. (1993). Transcriptional repression by the Drosophila even-skipped protein:definition of a minimal repression domain. Genes Dev.7, 491-503.
(
10.1101/gad.7.3.491
) -
Heid, P. J., Raich, W. B., Smith, R., Mohler, W. A., Simokat,K., Gendreau, S. B., Rothman, J. H. and Hardin, J. (2001). The zinc finger protein DIE-1 is required for late events during epithelial cell rearrangement in C. elegans. Dev. Biol.236,165-180.
(
10.1006/dbio.2001.0315
) -
Herrmann, B. G. (1995). The mouse Brachyury(T) gene. Semin. Dev. Biol.6, 385-394.
(
10.1016/S1044-5781(06)80002-2
) -
Ho, R. K. and Kane, D. A. (1990). Cell-autonomous action of zebrafish spt-1 mutation in specific mesodermal precursors. Nature348,728-730.
(
10.1038/348728a0
) -
Huang, X., Cheng, H. J., Tessier-Lavigne, M. and Jin, Y.(2002). MAX-1, a novel PH/MyTH4/FERM domain cytoplasmic protein implicated in netrin-mediated axon repulsion. Neuron34,563-576.
(
10.1016/S0896-6273(02)00672-4
) -
Hunter, C. P. and Kenyon, C. (1996). Spatial and temporal controls target PAL-1 blastomere specification activity to a single blastomere lineage in C. elegans embryos. Cell87,217-226.
(
10.1016/S0092-8674(00)81340-9
) -
Joly, J. S., Joly, C., Schulte-Merker, S., Boulekbache, H. and Condamine, H. (1993). The ventral and posterior expression of the zebrafish homeobox gene eve1 is perturbed in dorsalized and mutant embryos. Development119,1261-1275.
(
10.1242/dev.119.4.1261
) -
Kispert, A., Herrmann, B. G., Leptin, M. and Reuter, R.(1994). Homologs of the mouse Brachyury gene are involved in the specification of posterior terminal structures in Drosophila,Tribolium, and Locusta. Genes Dev.8,2137-2150.
(
10.1101/gad.8.18.2137
) -
Kispert, A., Koschorz, B. and Herrmann, B. G.(1995). The T protein encoded by Brachyury is a tissue-specific transcription factor. EMBO J.14,4763-4772.
(
10.1002/j.1460-2075.1995.tb00158.x
) - Kofron, M., Demel, T., Xanthos, J., Lohr, J., Sun, B., Sive, H.,Osada, S., Wright, C., Wylie, C. and Heasman, J. (1999). Mesoderm induction in Xenopus is a zygotic event regulated by maternal VegT via TGFbeta growth factors. Development126,5759-5770.
-
Kostas, S. A. and Fire, A. (2002). The T-box factor MLS-1 acts as a molecular switch during specification of nonstriated muscle in C. elegans. Genes Dev.16,257-269.
(
10.1101/gad.923102
) -
Kusch, T. and Reuter, R. (1999). Functions for Drosophila brachyenteron and forkhead in mesoderm specification and cell signalling. Development126,3991-4003.
(
10.1242/dev.126.18.3991
) -
Kusch, T., Storck, T., Walldorf, U. and Reuter, R.(2002). Brachyury proteins regulate target genes through modular binding sites in a cooperative fashion. Genes Dev.16,518-529.
(
10.1101/gad.213002
) -
Li, C. and Manley, J. L. (1998). Even-skipped represses transcription by binding TATA binding protein and blocking the TFIID-TATA box interaction. Mol. Cell Biol.18,3771-3781.
(
10.1128/MCB.18.7.3771
) - Mello, C. and Fire, A. (1995). DNA Transformation. In Caenorhabditis elegans: Modern Biological Analysis of an Organism. Vol. 48 (ed. D. Shakes and H. Epstein), pp. 451-482. San Diego:Academic Press.
-
Mohler, W. A., Simske, J. S., Williams-Masson, E. M., Hardin, J. D. and White, J. G. (1998). Dynamics and ultrastructure of developmental cell fusions in the Caenorhabditis elegans hypodermis. Curr. Biol.8,1087-1090.
(
10.1016/S0960-9822(98)70447-6
) -
Muller, C. W. and Herrmann, B. G. (1997). Crystallographic structure of the T domain-DNA complex of the Brachyury transcription factor. Nature389,884-888.
(
10.1038/39929
) -
Papaioannou, V. E. (2001). T-box genes in development: from hydra to humans. Int. Rev. Cytol.207, 1-70.
(
10.1016/S0074-7696(01)07002-4
) -
Pflugfelder, G. O. and Heisenberg, M. (1995). Optomotor-blind of Drosophila melanogaster: A neurogenetic approach to optic lobe development and optomotor behaviour. Comp. Biochem. Physiol. A Physiol.110,185-202.
(
10.1016/0300-9629(94)00159-Q
) - Rashbass, P., Wilson, V., Rosen, B. and Beddington, R. S.(1994). Alterations in gene expression during mesoderm formation and axial patterning in Brachyury (T) embryos. Int. J. Dev. Biol.38,35-44.
- Simmer, F., Tijsterman, M., Parrish, S., Koushika, S. P., Nonet,M. L., Fire, A., Ahringer, J. and Plasterk, R. H. (2002). Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi. Curr. Biol.12,1317-1319.
-
Simon, H.-G. (1999). T-box genes and the formation of vertebrate forelimb and hindlimb specific pattern. Cell Tissue Res.296,57-66.
(
10.1007/s004410051266
) -
Simske, J. S. and Hardin, J. (2001). Getting into shape: epidermal morphogenesis in Caenorhabditis elegansembryos. Bioessays23,12-23.
(
10.1002/1521-1878(200101)23:1<12::AID-BIES1003>3.0.CO;2-R
) -
Singer, J. B., Harbecke, R., Kusch, T., Reuter, R. and Lengyel,J. A. (1996). Drosophila brachyenteron regulates gene activity and morphogenesis in the gut. Development122,3707-3718.
(
10.1242/dev.122.12.3707
) -
Sinha, S., Abraham, S., Gronostajski, R. M. and Campbell, C. E. (2000). Differential DNA binding and transcription modulation by three T-box proteins, T, TBX1 and TBX2. Gene258,15-29.
(
10.1016/S0378-1119(00)00417-0
) -
Smith, J. (1999). T-box genes: what they do and how they do it. Trends Genet.15,154-158.
(
10.1016/S0168-9525(99)01693-5
) - Sulston, J. and Hodgkin, J. (1988). Methods. In The Nematode Caenorhabditis elegans (ed. W. B. Wood),pp. 587-606. New York: Cold Spring Harbor Laboratory Press.
-
Um, M., Li, C. and Manley, J. L. (1995). The transcriptional repressor even-skipped interacts directly with TATA-binding protein. Mol. Cell Biol.15,5007-5016.
(
10.1128/MCB.15.9.5007
) -
Woollard, A. and Hodgkin, J. (2000). The Caenorhabditis elegans fate-determining gene mab-9 encodes a T-box protein required to pattern the posterior hindgut. Genes Dev.14,596-603.
(
10.1101/gad.14.5.596
) -
Zhang, J., Houston, D. W., King, M. L., Payne, C., Wylie, C. and Heasman, J. (1998). The role of maternal VegT in establishing the primary germ layers in Xenopus embryos. Cell94,515-524.
(
10.1016/S0092-8674(00)81592-5
)
Dates
Type | When |
---|---|
Created | 21 years, 4 months ago (April 26, 2004, 8:23 p.m.) |
Deposited | 2 years, 4 months ago (April 28, 2023, 9:14 a.m.) |
Indexed | 1 month ago (Aug. 2, 2025, 12:11 a.m.) |
Issued | 21 years, 3 months ago (May 15, 2004) |
Published | 21 years, 3 months ago (May 15, 2004) |
Published Print | 21 years, 3 months ago (May 15, 2004) |
@article{Pocock_2004, title={A regulatory network of T-box genes and theeven-skippedhomologuevab-7controls patterning and morphogenesis inC. elegans}, volume={131}, ISSN={0950-1991}, url={http://dx.doi.org/10.1242/dev.01110}, DOI={10.1242/dev.01110}, number={10}, journal={Development}, publisher={The Company of Biologists}, author={Pocock, Roger and Ahringer, Julie and Mitsch, Michael and Maxwell, Sara and Woollard, Alison}, year={2004}, month=may, pages={2373–2385} }