NOGGIN ACTS DOWNSTREAM OF WNT AND SONIC HEDGEHOG TO ANTAGONIZE BMP4 IN AVIAN SOMITE PATTERNING

In the vertebrate embryo, the lateral compartment of the somite gives rise to muscles of the limb and body wall and is patterned in response to lateral-plate-derived BMP4. Activation of the myogenic program dis tinctive to the medial somite, i.e. relatively immediate development o f the epaxial muscle lineage, requires neutralization of this lateral signal, We have analyzed the properties of molecules likely to play a role in opposing lateral somite specification by BMP4. We propose that the BMP4 antagonist Noggin plays an important role in promoting media l somite patterning in vivo, We demonstrate that Noggin expression in the somite is under the control of a neural-tube-derived factor, whose effect can be mimicked experimentally by Wnt1, Wnt1 is appropriately expressed in the neural tube, Furthermore, we show that Sonic Hedgehog is able to activate ectopic expression of Noggin resulting in the blo cking of BMP4 specification of the lateral somite, Our results are con sistent with a model in which Noggin activation lies downstream of the SHH and Wnt signaling pathways.