Fig. 9. Model of possible Igu function in Hh signaling. (A) In wild-type embryos, Igu function is required for the positive and negative regulation of Gli protein function in response to Hh signals. Components in green have activating functions, and those in red have repressor functions. (B) Without the normal Igu/Dzip1 protein function (light blue), Hh-dependent regulation is lost and Gli proteins cannot fully activate the expression of Hh target genes. In addition, the negative regulation of Hh signaling is also reduced. igu mutations could act directly on PKA-mediated negative regulation of Hh signals (broken arrows and lines in B) and/or could act indirectly, possibly by causing the constitutive nuclear import of Gli proteins (thin arrows). The resulting constitutive, but weak, activating function of Gli proteins is sufficient to induce en1 and ptc1 in broad regions in somites. This same low level of activator function is not sufficient to activate genes such as nk2.2 in the ventral neural tube the transcription of which requires a higher level of Hh signals.