Morphogens regulate tissue patterning through their distribution in concentration gradients. Emerging research establishes a role for specialized signalling filopodia, or cytonemes, in morphogen dispersion and signalling. Previously we demonstrated that Hedgehog (Hh) morphogen is transported via vesicles along cytonemes emanating from signal-producing cells to form a gradient in Drosophila epit...

The intestinal epithelium undergoes a marked adaptive response following loss of functional small bowel surface area characterized by increased crypt cell proliferation and increased enterocyte migration from crypt to villus tip, resulting in villus hyperplasia and enhanced nutrient absorption. Hedgehog (Hh) signaling plays a critical role in regulating epithelial-mesenchymal interactions durin...

Sharp borders between cells with different developmental fates are important for patterning of invertebrates, but are not well understood in vertebrates. Zebrafish slow muscle cells develop from adaxial cells, a one-cell-diameter-thick pseudo-epithelium immediately adjacent to the notochord. Hedgehog (Hh) signals from notochord specify adaxial cells to form slow muscle cells. Cells next to adax...

The hedgehog (Hh) signaling pathway plays a central role during embryonic development, and its aberrant activation has been implicated in the development and progression of several human cancers. Major efforts toward the identification of chemical modulators of the hedgehog pathway have yielded several antagonists of the GPCR-like smoothened receptor. In contrast, potent inhibitors of the sonic...

Activation of Hedgehog (Hh) signaling requires the transmembrane protein Smoothened (Smo), a member of the G-protein coupled receptor superfamily. In mammals, Smo translocates to the primary cilium upon binding of Hh ligands to their receptor, Patched (Ptch1), but it is unclear if ciliary trafficking of Smo is sufficient for pathway activation. Here, we demonstrate that cyclopamine and jervine,...

Patched (Ptc) is the ligand-binding component of the Hedgehog (Hh) receptor complex. In the Drosophila embryo, Ptc and Hh colocalize in vesicular punctate structures. However, receptor-mediated endocytosis of Hh proteins has not been demonstrated. By using chick neural plate explants, we show that Sonic hedgehog (Shh)-responsive neural precursor cells internalize recombinant and endogenous Shh ...

Upshoot-in-adduction and downshoot-in-adduction are non-paretic motility disorders that usually accompany a horizontal squint in children, together with V- or A-pattern motility. Upshoot-in-adduction may sometime mimic a superior oblique palsy. The authors have found that even in healthy volunteers these motility disorders can be found and made manifest by patching. One eye of complaint-free vo...

Patterning of the vertebrate optic vesicle into proximal/optic stalk and distal/neural retina involves midline-derived Hedgehog (Hh) signalling, which promotes stalk specification. In the absence of Hh signalling, the stalks are not specified, causing cyclopia. Recent studies showed that the cell adhesion molecule Cdon forms a heteromeric complex with the Hh receptor Patched 1 (Ptc1). This rece...

Mutations in the Hedgehog receptor, Patched 1 (Ptch1), have been linked to both familial and sporadic forms of basal cell carcinoma (BCC), leading to the hypothesis that loss of Ptch1 function is sufficient for tumor progression. By combining conditional knockout technology with the inducible activity of the Keratin6 promoter, we provide in vivo evidence that loss of Ptch1 function from the bas...

AIMS Critical factors responsible for the recurrence of keratocystic odontogenic tumor (KCOT) were examined. METHODS The clinicopathological features were retrospectively studied in 74 patients with 75 sporadic KCOTs. From the 75 KCOTs, 23 were examined for the expression of Sonic Hedgehog (SHH), Patched and Smoothened (SMO) by immunohistochemistry. RESULTS Recurrence in multilocular lesion...