SWiP-1: novel SOCS box containing WD-protein regulated by signalling centres and by Shh during development

We describe a novel chick WD-protein, cSWiP-1, expressed in semitic mesoder m and developing limb buds as well as in other embryonic structures where H edgehog signalling has been shown to play a role. Using embryonic manipulat ions we show that in somites cSWiP-1 expression integrates two signals orig inating from structures adjacent to the segmental mesoderm: a positive sign al from the notochord and a negative signal from intermediate and/or latera l mesoderm. In explant cultures of semitic mesoderm, Shh protein induces cS WiP-1, while a blocking antibody to Shh inhibits the induction of cSWiP-1 b y the notochord. These results show that the positive signal from the notoc hord is mediated by Shh. We also show that in limb buds cSWiP-1 is upregula ted by ectopic Shh. This occurs in about the same time period as upregulati on of BMP2, placing cSWiP-1 among the earliest markers for the change of li mb pattern caused by ectopic Shh. We also describe a human homologue of cSW iP-1 and a mouse gene, mSWiP-2, that is more distantly related to SWiP-1, s uggesting that SWiP-1 belongs to a novel subfamily of WD-proteins. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.