PMID- 8269518 OWN - NLM STAT- MEDLINE DCOM- 19940131 LR - 20220409 IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 75 IP - 7 DP - 1993 Dec 31 TI - Sonic hedgehog mediates the polarizing activity of the ZPA. PG - 1401-16 AB - The zone of polarizing activity (ZPA) is a region at the posterior margin of the limb bud that induces mirror-image duplications when grafted to the anterior of a second limb. We have isolated a vertebrate gene, Sonic hedgehog, related to the Drosophila segment polarity gene hedgehog, which is expressed specifically in the ZPA and in other regions of the embryo, that is capable of polarizing limbs in grafting experiments. Retinoic acid, which can convert anterior limb bud tissue into tissue with polarizing activity, concomitantly induces Sonic hedgehog expression in the anterior limb bud. Implanting cells that express Sonic hedgehog into anterior limb buds is sufficient to cause ZPA-like limb duplications. Like the ZPA, Sonic hedgehog expression leads to the activation of Hox genes. Sonic hedgehog thus appears to function as the signal for antero-posterior patterning in the limb. FAU - Riddle, R D AU - Riddle RD AD - Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115. FAU - Johnson, R L AU - Johnson RL FAU - Laufer, E AU - Laufer E FAU - Tabin, C AU - Tabin C LA - eng SI - GENBANK/L20888 SI - GENBANK/L20889 SI - GENBANK/L26081 SI - GENBANK/L26082 SI - GENBANK/L26083 SI - GENBANK/L28099 SI - GENBANK/L33709 SI - GENBANK/S60904 SI - GENBANK/S60905 SI - GENBANK/S60924 PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (DNA Primers) RN - 0 (Drosophila Proteins) RN - 0 (Hedgehog Proteins) RN - 0 (Proteins) RN - 0 (RNA, Messenger) RN - 149291-21-4 (hh protein, Drosophila) RN - 5688UTC01R (Tretinoin) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Chick Embryo MH - DNA Primers/chemistry MH - *Drosophila Proteins MH - Embryonic Induction MH - Extremities/*embryology MH - Gene Expression/drug effects MH - Hedgehog Proteins MH - In Situ Hybridization MH - Molecular Sequence Data MH - Morphogenesis MH - Proteins/*genetics MH - RNA, Messenger/genetics MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - Tretinoin/pharmacology EDAT- 1993/12/31 00:00 MHDA- 1993/12/31 00:01 CRDT- 1993/12/31 00:00 PHST- 1993/12/31 00:00 [pubmed] PHST- 1993/12/31 00:01 [medline] PHST- 1993/12/31 00:00 [entrez] AID - 0092-8674(93)90626-2 [pii] AID - 10.1016/0092-8674(93)90626-2 [doi] PST - ppublish SO - Cell. 1993 Dec 31;75(7):1401-16. doi: 10.1016/0092-8674(93)90626-2.