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Patched receptors sense, interpret and establish an epidermal Hedgehog signalling gradient

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Item Type:Article
Title:Patched receptors sense, interpret and establish an epidermal Hedgehog signalling gradient
Creators Name:Adolphe, C. and Junker, J.P. and Lyubimova, A. and van Oudenaarden, A. and Wainwright, B.
Abstract:By employing the sensitivity of single molecule fluorescent in situ hybridisation (smFISH) we have precisely quantified the levels and defined the temporal and spatial distribution of Hedgehog signalling activity during embryonic skin development, and uncovered that there is a Hedgehog signalling gradient along the proximal-distal axis of developing hair follicles. In order to explore the contribution of Hedgehog receptors Ptch1 and Ptch2 in establishing the epidermal signalling gradient, we quantitated the level of pathway activity generated in Ptch1 and Ptch1;Ptch2-deficient skin and defined the contribution of each receptor to regulation of the levels of Hedgehog signalling identified in wild-type skin. Moreover, we show that both the cellular phenotype and level of pathway activity featured in Ptch1;Ptch2-deficient cells faithfully recapitulates the Peak level of endogenous Hedgehog signalling detected at the base of developing follicles, where the concentration of endogenous Shh is predicted to be highest. Taken together, these data demonstrate that both Ptch1 and Ptch2 play a crucial role in sensing the concentration of Hedgehog ligand and regulating the appropriate dose-dependent response.
Keywords:Animal Models, Cell Surface Receptors, Epidermis, Fluorescence In Situ Hybridization, Hedgehog Proteins, Patched Receptors, Patched-2 Receptor, Sensitivity and Specificity, Signal Transduction, Transgenic Mice, Animals, Mice
Source:Journal of Investigative Dermatology
Page Range:179-186
Date:January 2017
Official Publication:https://doi.org/10.1016/j.jid.2016.06.632
PubMed:View item in PubMed

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