title: A positive role for patched-smoothened signaling in promoting cell proliferation during normal head development in Drosophila.
abstract: The transmembrane receptor Patched regulates several developmental processes in both invertebrates and vertebrates. In vertebrates, Patched also acts as a tumor suppressor. The Patched pathway normally operates by negatively regulating Smoothened, a G-protein-coupled receptor; binding of Hedgehog ligand to Patched relieves this negative interaction and allows signaling by Smoothened. We show that Ptc regulates Drosophila head development by promoting cell proliferation in the eye-antennal disc. During head morphogenesis, Patched positively interacts with Smoothened, which leads to the activation of Activin type I receptor Baboon and stimulation of cell proliferation in the eye-antennal disc. Thus, loss of Ptc or Smoothened activity affects cell proliferation in the eye-antennal disc and results in adult head capsule defects. Similarly, reducing the dose of smoothened in a patched background enhances the head defects. Consistent with these results, gain-of-function Hedgehog interferes with the activation of Baboon by Patched and Smoothened, leading to a similar head capsule defect. Expression of an activated form of Baboon in the patched domain in a patched mutant background completely rescues the head defects. These results provide insight into head morphogenesis, a process we know very little about, and reveal an unexpected non-canonical positive signaling pathway in which Patched and Smoothened function to promote cell proliferation as opposed to repressing it.
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Baragur V
authors.initials: BV
authors.lastname: Shyamala
authors.forename: Krishna Moorthi
authors.initials: KM
authors.lastname: Bhat
mesh_terms: D000483:Alleles; D000818:Animals; D016923:Cell Death; D002455:Cell Division; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D005123:Eye / Q000196:embryology; D006257:Head / Q000254:growth & development; D053823:Hedgehog Proteins; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D010641:Phenotype; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction; D000072086:Smoothened Receptor
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; C032193:glycoprotein receptor GPIb-IX; C070844:ptc protein, Drosophila; C100664:smo protein, Drosophila; C077245:hh protein, Drosophila