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Development 129 (24): 5553-5566

hephaestus encodes a polypyrimidine tract binding protein that regulates Notch signalling during wing development in Drosophila melanogaster

David A. Dansereau1,2, Martine D. Lunke1, Ariel Finkielsztein2, Michael A. Russell2, and William J. Brook1,*

1 Genes and Development Research Group and Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada
2 Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6E 4G2, Canada

* Author for correspondence (e-mail: brook{at}ucalgary.ca)

Accepted for publication 10 September 2002.

Abstract: We describe the role of the Drosophila melanogaster hephaestus gene in wing development. We have identified several hephaestus mutations that map to a gene encoding a predicted RNA-binding protein highly related to human polypyrimidine tract binding protein and Xenopus laevis 60 kDa Vg1 mRNA-binding protein. Polypyrimidine tract binding proteins play diverse roles in RNA processing including the subcellular localization of mRNAs, translational control, internal ribosome entry site use, and the regulation of alternate exon selection. The analysis of gene expression in imaginal discs and adult cuticle of genetic mosaic animals supports a role for hephaestus in Notch signalling. Somatic clones lacking hephaestus express the Notch target genes wingless and cut, induce ectopic wing margin in adjacent wild-type tissue, inhibit wing-vein formation and have increased levels of Notch intracellular domain immunoreactivity. Clones mutant for both Delta and hephaestus have the characteristic loss-of-function thick vein phenotype of Delta. These results lead to the hypothesis that hephaestus is required to attenuate Notch activity following its activation by Delta. This is the first genetic analysis of polypyrimidine tract binding protein function in any organism and the first evidence that such proteins may be involved in the Notch signalling pathway.

Key Words: Notch signalling • hnRNP I • Delta • Serrate • Polypyrimidine tract binding protein (PTB) • RRM RNA-binding proteins • hephaestus

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