The graded response to sonic Hedgehog depends on cilia architecture Journal Article
| Authors: | Caspary, T.; Larkins, C. E.; Anderson, K. V. |
| Article Title: | The graded response to sonic Hedgehog depends on cilia architecture |
| Abstract: | Several studies have linked cilia and Hedgehog signaling, but the precise roles of ciliary proteins in signal transduction remain enigmatic. Here we describe a mouse mutation, hennin (hnn), that causes coupled defects in cilia structure and Sonic hedgehog (Shh) signaling. The hnn mutant cilia are short with a specific defect in the structure of the ciliary axoneme, and the hnn neural tube shows a Shh-independent expansion of the domain of motor neuron progenitors. The hnn mutation is a null allele of Arl13b, a small GTPase of the Arf/Arl family, and the Arl13b protein is localized to cilia. Double mutant analysis indicates that Gli3 repressor activity is normal in hnn embryos, but Gli activators are constitutively active at low levels. Thus, normal structure of the ciliary axoneme is required for the cell to translate different levels of Shh ligand into differential regulation of the Gli transcription factors that implement Hedgehog signals. © 2007 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; unclassified drug; gene mutation; mutation; exons; nonhuman; protein function; protein localization; animal cell; mouse; phenotype; animals; mice; allele; signaling; embryo; sonic hedgehog protein; hedgehog proteins; alleles; introns; gene product; embryo pattern formation; cell differentiation; mutational analysis; stem cell; gene expression regulation, developmental; oncogene proteins; gene repression; protein transport; ligands; cellbio; devbio; trans-activators; transcription factor pax6; arf protein; protein family; erinaceidae; receptors, g-protein-coupled; transcription factor gli3; eukaryotic flagellum; body patterning; cilia; protein patched 1; neural tube; motoneuron; cytoskeletal proteins; receptors, cell surface; axoneme; guanosine triphosphatase; neural tube defects; hennin; eye abnormalities; limb deformities, congenital |
| Journal Title: | Developmental Cell |
| Volume: | 12 |
| Issue: | 5 |
| ISSN: | 1534-5807 |
| Publisher: | Cell Press |
| Date Published: | 2007-05-08 |
| Start Page: | 767 |
| End Page: | 778 |
| Language: | English |
| DOI: | 10.1016/j.devcel.2007.03.004 |
| PUBMED: | 17488627 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 135" - "Export Date: 17 November 2011" - "CODEN: DCEEB" - "Source: Scopus" |
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