Products, genetic linkage and limb patterning activity of a murine hedgehog gene.
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.
Chang
D T
DT
Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
López
A
A
von Kessler
D P
DP
Chiang
C
C
Simandl
B K
BK
Zhao
R
R
Seldin
M F
MF
Fallon
J F
JF
Beachy
P A
PA
D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D002874:Chromosome Mapping; D017124:Conserved Sequence; D004330:Drosophila / Q000196:embryology / Q000235:genetics; D029721:Drosophila Proteins; D005121:Extremities / Q000196:embryology*; D005775:Gastrula / Q000502:physiology*; D008040:Genetic Linkage; D053823:Hedgehog Proteins; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D011784:Quail; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D011506:Proteins; C077245:hh protein, Drosophila