? ? The Hedgehog (Hh) family of secreted signaling proteins plays essential roles in coordinating cell growth and differentiation. Impaired pathway function in embryogenesis can produce severe malformations, such as cyclopia and other midline defects of the face and forebrain associated with deficits of Sonic hedgehog (Shh) signaling. In contrast to loss of Hh activity, inappropriate activation of the Shh signaling pathway has been associated with the formation of tumors. During normal development, Shh directly influences distant cells in the developing vertebrate limb and neural tube. The molecular mechanisms of this long-range Shh signaling are not entirely clear and have proven difficult to study in vivo. This proposal focuses on positive players necessary in mediating transport and long-range action of the Shh signal. Various approaches will be used to aid in discovery of novel pathway members associated with long-range signaling. Dorsoventral patterning of l the developing neural tube will serve as an in vivo model system to study the functions of these newly identified proteins in this important biological process. ? ? ?
