Products, genetic linkage and limb patterning activity of a murine hedgehog gene

David T. Chang, Alric Lopez, Doris P. Von Kessler, Chin Chiang, B. Kay Simandl, Renbin Zhao, Michael F Seldin, John F. Fallon, Philip A. Beachy

Research output: Contribution to journalArticle

259 Scopus citations

Abstract

The hedgehog (hh) segmentation gene of Drosophila melanogaster encodes a secreted signaling protein that functions in the patterning of larval and adult structures. Using low stringency hybridization and degenerate PCR primers, we have isolated complete or partial hh-like sequences from a range of invertebrate species including other insects, leech and sea urchin. We have also isolated three mouse and two human DNA fragments encoding distinct hh-like sequences. Our studies have focused upon Hhg-1, a mouse gene encoding a protein with 46% amino acid identity to hh. The Hhg-1 gene, which corresponds to the previously described vhh-1 or sonic class, is expressed in the notochord, ventral neural tube, lung bud, hindgut and posterior margin of the limb bud in developing mouse embryos. By segregation analysis the Hhg-1 gene has been localized to a region in proximal chromosome 5, where two mutations affecting mouse limb development previously have been mapped. In Drosophila embryos, ubiquitous expression of the Hhg-1 gene yields effects upon gene expression and cuticle pattern similar to those observed for the Drosophila hh gene. We also find that cultured quail cells transfected with a Hhg-1 expression construct can induce digit duplications when grafted to anterior or mid-distal but not posterior borders within the developing chick limb; more proximal limb element duplications are induced exclusively by mid-distal grafts. Both in transgenic Drosophila embryos and in transfected quail cells, the Hhg-1 protein product is cleaved to yield two stable fragments from a single larger precursor. The significance of Hhg-1 genetic linkage, patterning activity and proteolytic processing in Drosophila and chick embryos is discussed.

Original languageEnglish (US)
Pages (from-to)3339-3353
Number of pages15
JournalDevelopment
Volume120
Issue number11
StatePublished - Nov 1994
Externally publishedYes

Keywords

  • Gene expression
  • Genetic linkage
  • Hammertoe
  • Hedgehog
  • Hemimelic extra toes
  • Limb development
  • Mouse

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

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    Chang, D. T., Lopez, A., Von Kessler, D. P., Chiang, C., Simandl, B. K., Zhao, R., Seldin, M. F., Fallon, J. F., & Beachy, P. A. (1994). Products, genetic linkage and limb patterning activity of a murine hedgehog gene. Development, 120(11), 3339-3353.