Figure 7.

Proposed Model for Palatal Defects in Fuz Mutants

(A and B) Schematics depict E8.5 embryos. In Hedgehog signaling, anterograde transport delivers Gli3L (Gli3-activator) to the distal CLAMP-positive ciliary tip (red). Gli3-L is processed into Gli3-S (Gli3 repressor) which undergoes retrograde transport, repressing transcription of targets such as FGF8. Anterior NC (dark green) arises from the posterior mesencephalon and anterior hindbrain (purple), and is normally limited by a balance of Hh and FGF signals. NC then migrates into BA1, comprising maxillary and mandibular compartments (Mx and Md, respectively). When Fuz function is lost, ciliary transport and the distal compartment are severely disrupted leading to disruption of Gli processing and an expansion in cranial NC numbers, specifically maxillary NC.

(C–F) In (C) and (D), schematics depict coronal sections of E9.5 embryos. In coronal sections, the maxilla forms as two bilateral prominences and Fgf8 is expressed in lateral maxillary epithelia, indicated by purple in (C) through (F). In mutants, the maxillary compartment is enlarged and epithelial Fgf8 is expanded. In (E) and (F), schematics depict coronal sections of E10.5 embryos. Palatal condensations (red) are medial to FGF8 expression domains. In wild-type animals, these flank midline mesenchyme but remain separated. In Fuz mutants, expansion of FGF8 causes a medial shift of the palatal condensations. Subsequently, the normal bilateral palatal primordia join at the midline.