Boc and Gas1 Each Form Distinct Shh Receptor Complexes with Ptch1 and Are Required for Shh-Mediated Cell Proliferation

Izzi, Luisa; Lévesque, Martin; Morin, Steves; Laniel, Dominique; Wilkes, Brian C.; Mille, Frédéric; Krauss, Robert M.; McMahon, Andrew P.; Allen, Benjamin L.; Charron, Frédéric

doi:10.1016/j.devcel.2011.04.017

Cited by 225 publications

(257 citation statements)

References 40 publications

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“…Cdo is expressed in retinal neurons but has no apparent roles (36), whereas Gas1 is required earlier to pattern the neural retina (37). Furthermore, Gas1, Boc, and Cdo act cooperatively in several Hh-mediated embryonic patterning events, but they also show unique prevalence for each specific compound mutant phenotype depending on dosage and expression (38,39). Thus, Shh employs Gas1, Cdo, and/or Boc in a context-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Gas1 is a receptor for sonic hedgehog to repel enteric axons

Jin

Martinelli

Zheng

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The myenteric plexus of the enteric nervous system controls the movement of smooth muscles in the gastrointestinal system. They extend their axons between two peripheral smooth muscle layers to form a tubular meshwork arborizing the gut wall. How a tubular axonal meshwork becomes established without invading centrally toward the gut epithelium has not been addressed. We provide evidence here that sonic hedgehog (Shh) secreted from the gut epithelium prevents central projections of enteric axons, thereby forcing their peripheral tubular distribution. Exclusion of enteric central projections by Shh requires its binding partner growth arrest specific gene 1 (Gas1) and its signaling component smoothened (Smo) in enteric neurons. Using enteric neurons differentiated from neurospheres in vitro, we show that enteric axon growth is not inhibited by Shh. Rather, when Shh is presented as a point source, enteric axons turn away from it in a Gas1-dependent manner. Of the Gαi proteins that can couple with Smo, G protein α Z (Gnaz) is found in enteric axons. Knockdown and dominant negative inhibition of Gnaz dampen the axon-repulsive response to Shh, and Gnaz mutant intestines contain centrally projected enteric axons. Together, our data uncover a previously unsuspected mechanism underlying development of centrifugal tubular organization and identify a previously unidentified effector of Shh in axon guidance.enteric neuron | axon guidance | chemorepellent | Hedgehog | Gas1

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Section: Discussionmentioning

confidence: 99%

Gas1 is a receptor for sonic hedgehog to repel enteric axons

Jin

Martinelli

Zheng

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Dorsal progenitors in LDA mutants ultimately experience high levels of SHH, as indicated by FOXA2 and NKX2.2 expression; however, dorsal cells may not receive this signal within the narrow early competence window required for definitive floorplate specification (Ribes et al, 2010). Last, additional HH-binding proteins may limit the time and range of SHH ligand-based responses, including the HH co-receptors GAS1, CDON and BOC Izzi et al, 2011), glypicans (Capurro et al, 2008;Li et al, 2011), megalin (LRP2) (Christ et al, 2012), or other cell-surface proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, the collective action of PTCH1, PTCH2 and HHIP1 to restrict HH pathway activity is analogous to the general requirement for the HH co-receptors GAS1, CDON and BOC to activate HH signaling Izzi et al, 2011). Similarly, removal of a single co-receptor produces only minor defects in ventral neural patterning while combined removal of GAS1, CDON and BOC reveals their collective requirement in ligand-mediated HH pathway…”

Section: Complexity Of Cell Surface Regulation Of Hh Signaling Duringmentioning

confidence: 99%

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Essential role for ligand-dependent feedback antagonism of vertebrate hedgehog signaling by PTCH1, PTCH2 and HHIP1 during neural patterning

et al. 2013

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SUMMARYHedgehog (HH) signaling is essential for vertebrate and invertebrate embryogenesis. In Drosophila, feedback upregulation of the HH receptor Patched (PTC; PTCH in vertebrates), is required to restrict HH signaling during development. By contrast, PTCH1 upregulation is dispensable for early HH-dependent patterning in mice. Unique to vertebrates are two additional HH-binding antagonists that are induced by HH signaling, HHIP1 and the PTCH1 homologue PTCH2. Although HHIP1 functions semi-redundantly with PTCH1 to restrict HH signaling in the developing nervous system, a role for PTCH2 remains unresolved. Data presented here define a novel role for PTCH2 as a ciliary localized HH pathway antagonist. While PTCH2 is dispensable for normal ventral neural patterning, combined removal of PTCH2-and PTCH1-feedback antagonism produces a significant expansion of HH-dependent ventral neural progenitors. Strikingly, complete loss of PTCH2-, HHIP1-and PTCH1-feedback inhibition results in ectopic specification of ventral cell fates throughout the neural tube, reflecting constitutive HH pathway activation. Overall, these data reveal an essential role for liganddependent feedback inhibition of vertebrate HH signaling governed collectively by PTCH1, PTCH2 and HHIP1.

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“…During postnatal cerebellar development, both glial astrocytes and GCPs express high levels of the Shh pathway components, including the transmembrane transporter-like patched 1 (Ptch1) and the seventransmembrane span smoothened (Smo) proteins (10,11). Shh signaling is regulated by several ligand-binding factors, including Ptch1, its primary receptor, and associated coreceptors (12,13). The binding of Shh to the Ptch1 complex leads to the derepression of Smo.…”

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confidence: 99%

Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor

Marazziti

Pietro

Golini

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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In the developing cerebellum, the proliferation and differentiation of glial and neuronal cell types depend on the modulation of the sonic hedgehog (Shh) signaling pathway. The vertebrate Gprotein-coupled receptor 37-like 1 (GPR37L1) gene encodes a putative G-protein-coupled receptor that is expressed in newborn and adult cerebellar Bergmann glia astrocytes. This study shows that the ablation of the murine Gpr37l1 gene results in premature down-regulation of proliferation of granule neuron precursors and precocious maturation of Bergmann glia and Purkinje neurons. These alterations are accompanied by improved adult motor learning and coordination. Gpr37l1 −/− mice also exhibit specific modifications of the Shh signaling cascade. Specific assays show that in Bergmann glia cells Gpr37l1 is associated with primary cilium membranes and it specifically interacts and colocalizes with the Shh primary receptor, patched 1. These findings indicate that the patched 1-associated Gpr37l1 receptor participates in the regulation of postnatal cerebellum development by modulating the Shh pathway.mutant mouse model | mitogenic signaling

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Boc and Gas1 Each Form Distinct Shh Receptor Complexes with Ptch1 and Are Required for Shh-Mediated Cell Proliferation

Cited by 225 publications

References 40 publications

Gas1 is a receptor for sonic hedgehog to repel enteric axons

Gas1 is a receptor for sonic hedgehog to repel enteric axons

Essential role for ligand-dependent feedback antagonism of vertebrate hedgehog signaling by PTCH1, PTCH2 and HHIP1 during neural patterning

Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor

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