The Drosophila dorsal-ventral patterning gene tolloid is related to human bone morphogenetic protein 1

Mary Jane Shimell, Edwin L. Ferguson, Steven R. Childs, Michael B. O'Connor

Research output: Contribution to journalArticlepeer-review

245 Scopus citations

Abstract

Mutations in the Drosophila tolloid (tld) gene lead to a partial transformation of dorsal ectoderm into ventral ectoderm. The null phenotype of tld is similar to, but less severe than decapentaplegic (dpp), a TGF-β family member required for the formation of all dorsal structures. We have cloned the tld locus by P element tagging. At the blastoderm stage, tld RNA is expressed dorsally, similar to that described for dpp. Analysis of a tld cDNA reveals three sequence motifs: an N terminal region of similarity to a metalloprotease, two EGF-like repeats, and five copies of a repeat found in human complement proteins C1r and C1s. tld sequence is 41% identical to human bone morphogenetic protein 1 (BMP-1); the closest members to dpp within the TGF-β superfamily are BMP-2 and BMP-4, two other bone morphogenetic proteins. These findings suggest that these genes are members of a signal generating pathway that has been conserved between insects and mammals.

Original languageEnglish (US)
Pages (from-to)469-481
Number of pages13
JournalCell
Volume67
Issue number3
DOIs
StatePublished - Nov 1 1991
Externally publishedYes

Bibliographical note

Funding Information:
We wish to acknowledge Eileen Kimm for her assistance in analyzing the nested t/d deletions and Martin Smith for the generous time and advice he gave us when using his IBI Sequencing System. We thank Yishi Jin for contribution of a developmental Northern blot, and Rob Ray and Francesca Pignoni for advice on in situ hybridization to whole-mount embryos. We are grateful to Nigel Atkinson for supplying the s/o? stock. We thank Bill Gelbart for initially bringing BMP-1 to our attention, and we are grateful to Kathryn Anderson Larry Marsh, Mark Peifer, and Jeff Simon for critical evaluation of the manuscript. This work was supported by awards from the Academic Senate of UC Irvine, the Cancer Research Coordinating Committee of the University of California, and P. H. S. grant GM42546 to M. B. 0. E. L. F. was supported by a Helen Hay Whitney fellowship, a NIH postdoctoral training grant, HD07299. and by P. H. S. grant GM35437 to Kathryn Anderson.

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