A Mammalian patched Homolog Is Expressed in Target Tissues of sonic hedgehog and Maps to a Region Associated with Developmental Abnormalities

doi:10.1074/jbc.271.21.12125

A Mammalian patched Homolog Is Expressed in Target Tissues of sonic hedgehog and Maps to a Region Associated with Developmental Abnormalities (*)

From the (1) Human Genetics Section, Laboratory of Viral Carcinogenesis and the
(2) Intramural Research Support Program, Scientific Applications International Corporation Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, the
(3) Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia 4072, Australia, the
(4) Department of Bioscience, Center for Nutrition and Toxicology, Karolinska Institute, S-171 57 Huddinge, Sweden, and the
(5) Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520

^§ To whom correspondence should be addressed. Tel.: 301-846-5931; Fax: 301-846-1909; dean{at}fcrfv1.ncifcrf.gov.

Abstract

Drosophila patched is a segment polarity gene required for the correct patterning of larval segments and imaginal discs during fly development and has a close functional relationship with hedgehog. We have isolated a complete human PATCHED cDNA sequence, which encodes a putative protein of 1296 amino acids, and displays 39% identity and 60% similarity to the Drosophila PATCHED protein. Hydropathy analysis suggests that human PATCHED is an integral membrane protein with a pattern of hydrophobic and hydrophilic stretches nearly identical to that of Drosophila patched. In the developing mouse embryo, patched is initially detected within the ventral neural tube and later in the somites and limb buds. Expression in the limb buds is restricted to the posterior ectoderm surrounding the zone of polarizing activity. The results show that patched is expressed in target tissues of sonic hedgehog, a murine homolog of Drosophila hedgehog suggesting that patched/hedgehog interactions have been conserved during evolution. Human PATCHED maps to human chromosome 9q22.3, the candidate region for the nevoid basal cell carcinoma syndrome. Patched expression is compatible with the congenital defects observed in the nevoid basal cell carcinoma syndrome.

Footnotes

↵* This work was supported by a grant from the Australian National Health and Medical Research Council (to B. W. and C. A. W.) and grants from the Swedish Cancer Fund, Swedish Radiation Protection Institute, and Edvard Welanders Stiftelse (to P. G. Z., I. V., and R. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank ™/EMBL Data Bank with accession number(s) U43148[GenBank].
↵() The abbreviations used are:

ptc

patched

NBCCS

nevoid basal cell carcinoma syndrome

PCR

polymerase chain reaction

YAC

yeast artificial chromosome

dpc

days post-coitus

kb

kilobase pair(s)

ORF

open reading frame.
- Received January 31, 1996.
- Revision received March 26, 1996.