Fig. 2. Possible ways in which megalin might influence N-Shh trafficking and signaling. The mechanisms include direct signaling via megalin [the asterisk indicates megalin-binding adaptor proteins of the fetal brain (Petersen et al., 2003)], megalin-mediated endocytosis and trafficking of N-Shh leading to N-Shh transcytosis and megalin-mediated trafficking of the N-Shh receptors Ptc and Smo. Not depicted in the model are heparan sulfate proteoglycans, which have been shown to cooperate with megalin in N-Shh endocytosis (McCarthy et al., 2002).