Identification of sonic hedgehog-responsive genes using cDNA microarray.
Sonic hedgehog (Shh) is a secreted signaling protein that plays important roles in a variety of developmental processes and also in pathogenesis of some human cancers and congenital diseases. Molecules that function downstream of Shh, however, still remain elusive. Here we searched for Shh-responsive genes by using an in-house cDNA microarray. Two genes were newly identified to be Shh responsive in neuroepithelial cell line MNS-70: the metal-binding protein Ceruloplasmin (Cp) and the serine protease inhibitor inter-alpha-trypsine inhibitor heavy chain H3 (ITIH3). In MNS-70 cells, expression of ITIH3 was regulated by Gli zinc-finger transcription factors downstream of Shh, whereas Cp appeared to be regulated by Gli-independent pathways. Cp mRNA was detected in the developing mouse brain, where its expression domain was closely adjacent to that of Shh. These results demonstrate that microarray technology provides a useful tool for studying expression of developmentally regulated genes.
Kato
M
M
Division of Signal Transduction, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-01, Japan.
Seki
N
N
Sugano
S
S
Hashimoto
K
K
Masuho
Y
Y
Muramatsu
M
M
Kaibuchi
K
K
Nakafuku
M
M
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002460:Cell Line; D002570:Ceruloplasmin / Q000235:genetics; D018076:DNA, Complementary / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008813:Mice, Inbred ICR; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection; D014361:Trypsin Inhibitors / Q000235:genetics*; D016335:Zinc Fingers
D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D053823:Hedgehog Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; C509239:SHH protein, human; D015534:Trans-Activators; D014361:Trypsin Inhibitors; C061151:pre-alpha-trypsin inhibitor; D002570:Ceruloplasmin; D012697:Serine Endopeptidases