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PMID: 12372301 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched.

Cell ·Vol. 111 ·No. 1 ·2002-10-04 ·Pages 63-75

Ma Y, Erkner A, Gong R, Yao S, Taipale J, Basler K, Beachy PA

Abstract

The dispatched (disp) gene is required for long-range Hedgehog (Hh) signaling in Drosophila. Here, we demonstrate that one of two murine homologs, mDispA, can rescue disp function in Drosophila and is essential for all Hh patterning activities examined in the early mouse embryo. Embryonic fibroblasts lacking mDispA respond normally to exogenously provided Sonic hedgehog (Shh) signal, but are impaired in stimulation of other responding cells when expressing Shh. We have developed a biochemical assay that directly measures the activity of Disp proteins in release of soluble Hh proteins. This activity is disrupted by alteration of residues functionally conserved in Patched and in a related family of bacterial transmembrane transporters, thus suggesting similar mechanisms of action for all of these proteins.

MeSH Terms

Alleles Amino Acid Motifs Amino Acid Sequence Animals Biological Transport Body Patterning Cell Membrane/metabolism Cloning, Molecular DNA, Complementary/metabolism Drosophila Drosophila Proteins/metabolism Embryo, Mammalian/metabolism Embryo, Nonmammalian Exons Expressed Sequence Tags Fibroblasts/metabolism Hedgehog Proteins Immunohistochemistry In Situ Hybridization Membrane Proteins/physiology Mice Mice, Inbred C57BL Models, Biological Models, Genetic Molecular Sequence Data Mutation Neural Crest/pathology Phenotype Prosencephalon/pathology,ultrastructure Sequence Homology, Amino Acid Signal Transduction Time Factors Trans-Activators/metabolism beta-Galactosidase/metabolism

Chemicals

DNA, Complementary Drosophila Proteins Hedgehog Proteins Membrane Proteins Trans-Activators disp protein, Drosophila hh protein, Drosophila beta-Galactosidase

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

Ma Yong

Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Erkner Alfrun

Gong Ruoyu

Yao Shenqin

Taipale Jussi

Basler Konrad

Beachy Philip A

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(02)00977-7

Published

2002-10-04

Pages

63-75

Language

English

Region

United States

NLM ID

0413066

Subset

External Links

PubMed source DOI: 10.1016/s0092-8674(02)00977-7 View journal details

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Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched.

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