Proteins of the Hedgehog, Wnt and Epidermal Growth Factor Receptor (EGFR) ligand families are secreted signals that induce concentration-dependent responses in surrounding cells. Although these proteins must diffuse through the aqueous extracellular environment, recent work has shown that hydrophobic lipid modifications are essential for their functions. All three classes of ligands are palmito...

Compartmentalization within cells provides spatial organization of signaling pathways and ensures the specificity of signaling. In vertebrates, the primary cilium, a tiny microtubule-based protrusion present on most cells, is essential for organizing events during Hedgehog signal transduction. When cells are stimulated with Hedgehog ligands, proteins in the pathway move in and out of the cilia....

Morphogens control patterns of transcription in development, often by establishing concentration gradients of a single transcriptional activator. However, many morphogens, including Hedgehog, create opposing activator and repressor gradients (OARGs). In contrast to single activator gradients, it is not well understood how OARGs control transcriptional patterns. We present a general thermodynami...

The cortex and basal ganglia are the major structures of the adult brain derived from the embryonic telencephalon. Two morphologically distinct regions of the basal ganglia are evident within the mature ventral telencephalon, the globus pallidus medially, and the striatum, which is positioned between the globus pallidus and the cortex. Deletion of the Sonic Hedgehog gene in mice indicates that ...

Hedgehog signaling has been implicated in the development of several human cancers, including small cell lung carcinomas, medulloblastomas, basal cell carcinomas, and digestive tract tumors. Elevated levels of pathway components are observed in pancreatic ductal adenocarcinoma (PDAC) precursor lesions, and these levels increase further as lesions progress to more advanced stages. Yet the mechan...

Ci/Gli zinc finger proteins mediate the transcriptional effects of Hedgehog protein signals. In Drosophila, Ci action as transcriptional repressor or activator is contingent upon Hedgehog-regulated, PKA-dependent proteolytic processing. We demonstrate that PKA-dependent processing of vertebrate Gli3 in developing limb similarly generates a potent repressor in a manner antagonized by apparent lo...

The Hedgehog signaling pathway is part of the ancient developmental-evolutionary animal toolkit. Frequently co-opted to pattern new structures, the pathway is conserved among eumetazoans yet flexible and pleiotropic in its effects. The Hedgehog receptor, Patched, is transcriptionally activated by Hedgehog, providing essential negative feedback in all tissues. Our locus-wide dissections of the c...

We suggest that the gauge-invariant hedgehoglike structures in the Wilson loops are physically interesting degrees of freedom in the Yang–Mills theory. The trajectories of these “hedgehog loops” are closed curves corresponding to center-valued (untraced) Wilson loops and are characterized by the center charge and winding number. We show numerically in the SU(2) Yang–Mills theory that the densit...

Midline signaling by Hedgehog (Hh) family members has been implicated in patterning the vertebrate embryo. We have explored the potential regulatory role of cAMP-dependent protein kinase A (PKA) in these events. Zebrafish embryos injected with RNAs encoding Sonic hedgehog (Shh), Indian hedgehog (Ihh), or a dominant-negative regulatory subunit of PKA, PKI, have equivalent phenotypes. These inclu...

Gene duplication is thought to provide raw material for functional divergence and innovation. Fish-specific dmrt2b has been identified as a duplicated gene of the dmrt2a/terra in fish genomes, but its function has remained unclear. Here we reveal that Dmrt2b knockdown zebrafish embryos display a downward tail curvature and have U-shaped somites. Then, we demonstrate that Dmrt2b contributes to a...