Hedgehog Signaling Regulates Transcription Through Cubitus Interruptus, a Sequence-specific DNA Binding Protein

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1997 Mar 18

PMID 9122207

Citations 34

Authors

T Von Ohlen

D Lessing

R Nusse

J E HOOPER

Affiliations

Soon will be listed here.

Abstract

Hedgehog (Hh) is a member of a family of secreted proteins that direct patterning at multiple stages in both Drosophila and vertebrate development. During Drosophila embryogenesis, Hh protein is secreted by the cells of the posterior compartment of each segment. hh activates transcription of wingless (wg), gooseberry (gsb), and patched (ptc) in the cells immediately adjacent to Hh-secreting cells. Hh signaling is thought to involve the segment polarity gene cubitus interruptus (ci). ci encodes a zinc finger protein of the Gli family of sequence-specific DNA binding proteins. ci mRNA is expressed in all non-Hh expressing cells. Here we demonstrate ci activity is both necessary and sufficient to drive expression of Hh-responsive genes in the Drosophila embryos. We show that Ci is a sequence-specific DNA binding protein that drives transcription from the wg promoter in transiently transfected cells. We demonstrate that Ci binding sites in the wg promoter are necessary for this transcriptional activation. These data taken together provide strong evidence that Ci is a transcriptional effector of Hh signaling.

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References

Smith D, Johnson K . Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988; 67(1):31-40. DOI: 10.1016/0378-1119(88)90005-4. View

Capdevila J, Guerrero I . Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. EMBO J. 1994; 13(19):4459-68. PMC: 395378. DOI: 10.1002/j.1460-2075.1994.tb06768.x. View

HOOPER J, Scott M . The Drosophila patched gene encodes a putative membrane protein required for segmental patterning. Cell. 1989; 59(4):751-65. DOI: 10.1016/0092-8674(89)90021-4. View

Alexandre C, Jacinto A, Ingham P . Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins. Genes Dev. 1996; 10(16):2003-13. DOI: 10.1101/gad.10.16.2003. View

Kinzler K, Vogelstein B . The GLI gene encodes a nuclear protein which binds specific sequences in the human genome. Mol Cell Biol. 1990; 10(2):634-42. PMC: 360861. DOI: 10.1128/mcb.10.2.634-642.1990. View

Heberlein U, Singh C, Luk A, Donohoe T . Growth and differentiation in the Drosophila eye coordinated by hedgehog. Nature. 1995; 373(6516):709-11. DOI: 10.1038/373709a0. View

Slusarski D, Motzny C, Holmgren R . Mutations that alter the timing and pattern of cubitus interruptus gene expression in Drosophila melanogaster. Genetics. 1995; 139(1):229-40. PMC: 1206321. DOI: 10.1093/genetics/139.1.229. View

Heemskerk J, DiNardo S . Drosophila hedgehog acts as a morphogen in cellular patterning. Cell. 1994; 76(3):449-60. DOI: 10.1016/0092-8674(94)90110-4. View

Nordeen S . Luciferase reporter gene vectors for analysis of promoters and enhancers. Biotechniques. 1988; 6(5):454-8. View

10.

Ma C, Moses K . Wingless and patched are negative regulators of the morphogenetic furrow and can affect tissue polarity in the developing Drosophila compound eye. Development. 1995; 121(8):2279-89. DOI: 10.1242/dev.121.8.2279. View

11.

HOOPER J . Distinct pathways for autocrine and paracrine Wingless signalling in Drosophila embryos. Nature. 1994; 372(6505):461-4. DOI: 10.1038/372461a0. View

12.

Ruppert J, Vogelstein B, Arheden K, Kinzler K . GLI3 encodes a 190-kilodalton protein with multiple regions of GLI similarity. Mol Cell Biol. 1990; 10(10):5408-15. PMC: 361243. DOI: 10.1128/mcb.10.10.5408-5415.1990. View

13.

Kinzler K, Ruppert J, Bigner S, Vogelstein B . The GLI gene is a member of the Kruppel family of zinc finger proteins. Nature. 1988; 332(6162):371-4. DOI: 10.1038/332371a0. View

14.

Ingham P, Taylor A, Nakano Y . Role of the Drosophila patched gene in positional signalling. Nature. 1991; 353(6340):184-7. DOI: 10.1038/353184a0. View

15.

DE Wet J, Wood K, DeLuca M, Helinski D, Subramani S . Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987; 7(2):725-37. PMC: 365129. DOI: 10.1128/mcb.7.2.725-737.1987. View

16.

Orenic T, Slusarski D, Kroll K, Holmgren R . Cloning and characterization of the segment polarity gene cubitus interruptus Dominant of Drosophila. Genes Dev. 1990; 4(6):1053-67. DOI: 10.1101/gad.4.6.1053. View

17.

Johnson R, Grenier J, Scott M . patched overexpression alters wing disc size and pattern: transcriptional and post-transcriptional effects on hedgehog targets. Development. 1995; 121(12):4161-70. DOI: 10.1242/dev.121.12.4161. View

18.

Baker N . Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos. EMBO J. 1987; 6(6):1765-73. PMC: 553553. DOI: 10.1002/j.1460-2075.1987.tb02429.x. View

19.

Brown N, Kafatos F . Functional cDNA libraries from Drosophila embryos. J Mol Biol. 1988; 203(2):425-37. DOI: 10.1016/0022-2836(88)90010-1. View

20.

Perrimon N . The genetic basis of patterned baldness in Drosophila. Cell. 1994; 76(5):781-4. DOI: 10.1016/0092-8674(94)90351-4. View