Balancing Hedgehog, a retention and release equilibrium given by Dally, Ihog, Boi and shifted/DmWif

Bilioni, Aphrodite; Sánchez‐Hernández, D.; Callejo, Ainhoa; Gradilla, Ana-Citlali; Ibáñez, Carmen; Mollica, Emanuela; Rodríguez-Navas, M. Carmen; Simon, Eléanor; Guerrero, Isabel

doi:10.1016/j.ydbio.2012.12.013

Cited by 67 publications

(162 citation statements)

References 67 publications

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“…In vertebrate Hh proteins, heparan sulfate is mainly bound by the Cardin-Weintraub motif BBBxxBB (B represents a basic amino acid, x represents any amino acid) (Cardin and Weintraub, 1989;Chang et al, 2011;Farshi et al, 2011;Rubin et al, 2002), but Cardin-Weintraub residues also constitute the Nterminal Hh sheddase cleavage site (Ohlig et al, 2012). This suggests a possible mode of processing regulation by competitive heparan sulfate binding, consistent with recently described HSPG bioactivities in Hh-producing cells (Ayers et al, 2010;Bilioni et al, 2013;Oustah et al, 2014;Wojcinski et al, 2011). In the present study, we provide evidence that supports this functional link.…”

Section: Introductionsupporting

confidence: 81%

Sonic hedgehog processing and release are regulated by glypican heparan sulfate proteoglycans

Ortmann,

Pickhinke,

Exner

et al. 2015

Journal of Cell Science

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There was an error published in J. Cell Sci. 128, 2374-2385.The reference Oustah et al. (2014) was cited incorrectly throughout the manuscript and in the reference list. Citations of Oustah et al. (2014) should read Al Oustah et al. (2014), and the correct reference is given below.Al Oustah, A., Danesin, C., Khouri-Farah, N., Farreny, M.-A., Escalas, N., Cochard, P., Glise, B. and Soula, C. (2014 show that glypican heparan sulfate proteoglycans regulate this process, through their heparan sulfate chains, in a cell autonomous manner. Heparan sulfate specifically modifies Shh processing at the cell surface, and purified glycosaminoglycans enhance the proteolytic removal of N-and C-terminal Shh peptides under cellfree conditions. The most likely explanation for these observations is direct Shh processing in the extracellular compartment, suggesting that heparan sulfate acts as a scaffold or activator for Shh ligands and the factors required for their turnover. We also show that purified heparan sulfate isolated from specific cell types and tissues mediates the release of bioactive Shh from pancreatic cancer cells, revealing a previously unknown regulatory role for these versatile molecules in a pathological context.

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Section: Introductionsupporting

confidence: 81%

Sonic hedgehog processing and release are regulated by glypican heparan sulfate proteoglycans

Ortmann,

Pickhinke,

Exner

et al. 2015

Journal of Cell Science

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“…Basal cytonemes that also orient perpendicular to the A/P axis, but differ from the apical cytonemes in composition and shape, were also described, but their function was not known. The Guerrero group has, more recently, shown that basal cytonemes traffic Hh (Bilioni et al, 2013;Bischoff et al, 2013;Callejo et al, 2011), giving further support to the idea that cells make multiple types of cytonemes that are tailored to specific signaling pathways (Roy et al, 2011).…”

Section: Direct Imaging Of Functional Hh Proteinmentioning

confidence: 88%

“…The Guerrero group reported that basal cytonemes emanating from both A and P cells can be visualized with various membrane and cytoskeletal markers under conditions of Ihog overexpression (Bilioni et al, 2013;Bischoff et al, 2013;Callejo et al, 2011), and showed that several Hh pathway components mark cytonemes as well. Our observations with BAC-encoded Hh:GFP and Ptc: mCherry also suggest cytoneme-mediated trafficking that involves direct transfer of Hh to A compartment cytonemes.…”

Section: Direct Imaging Of Functional Hh Proteinmentioning

confidence: 99%

“…Disc cells also have cytonemes that extend from the basolateral membrane that have been implicated in Hh signaling (Callejo et al, 2011). These basolateral cytonemes mostly orient toward the A/P compartment border (Callejo et al, 2011;Roy et al, 2011), and some extend across the A/P border and appear to transport Hh to A compartment cells in motile puncta (Bilioni et al, 2013;Bischoff et al, 2013;Callejo et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc

et al. 2017

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Morphogen concentration gradients that extend across developmental fields form by dispersion from source cells. In the Drosophila wing disc, Hedgehog (Hh) produced by posterior compartment cells distributes in a concentration gradient to adjacent cells of the anterior compartment. We monitored Hh:GFP after pulsed expression, and analyzed the movement and colocalization of Hh, Patched (Ptc) and Smoothened (Smo) proteins tagged with GFP or mCherry and expressed at physiological levels from bacterial artificial chromosome transgenes. Hh:GFP moved to basal subcellular locations prior to release from posterior compartment cells that express it, and was taken up by basal cytonemes that extend to the source cells. Hh and Ptc were present in puncta that moved along the basal cytonemes and formed characteristic apical-basal distributions in the anterior compartment cells. The basal cytonemes required diaphanous, SCAR, Neuroglian and Synaptobrevin, and both the Hh gradient and Hh signaling declined under conditions in which the cytonemes were compromised. These findings show that in the wing disc, Hh distributions and signaling are dependent upon basal release and uptake, and on cytoneme-mediated movement. No evidence for apical dispersion was obtained.

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“…15 Alternatively, Hh would be secreted apically and then released basolaterally with a complex choreography to board cytonemes that originate from the Hh-producing cells. 16,17 A third model proposed by Palm et al is that both cholesterol-bound Hh and cholesterol-free Hh could be secreted, and act in synergy although the putative mechanism that generate cholesterol-free Hh is unknown. 11 Thus, how can we reconcile all these mutually exclusive mechanisms to explain how Hh gradient is generated in the wing disc?…”

mentioning

confidence: 99%