Patched Receptors Sense, Interpret, and Establish an Epidermal Hedgehog Signaling Gradient

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• 作者：Christelle Adolphe¹ ; ⁴ ; Jan Philipp Junker² ; ³ ; ⁴ ; Anna Lyubimova² ; Alexander van Oudenaarden² ; Brandon Wainwright¹ ; ^{b.wainwright@imb.uq.edu.au}
• 关键词：BCC ; basal cell carcinoma ; E ; embryonic day ; HF ; hair follicle ; Hh ; Hedgehog ; IFE ; interfollicular epidermis ; K ; keratin ; LDA ; ligand-dependent antagonism ; LIA ; ligand-independent antagonism ; Shh ; Sonic Hedgehog ; smFISH ; single-molecule fluorescent in situ hybridization
• 刊名：Journal of Investigative Dermatology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：137
• 期：1
• 页码：179-186
• 全文大小：2278 K
• 卷排序：137

文摘

By using the sensitivity of single-molecule fluorescent in situ hybridization, we have precisely quantified the levels and defined the temporal and spatial distribution of Hedgehog signaling activity during embryonic skin development and discovered that there is a Hedgehog signaling gradient along the proximal-distal axis of developing hair follicles. To explore the contribution of Hedgehog receptors Ptch1 and Ptch2 in establishing the epidermal signaling 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 signaling 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 signaling detected at the base of developing follicles, where the concentration of endogenous Shh is predicted to be highest. Taken together, these data show that both Ptch1 and Ptch2 play a crucial role in sensing the concentration of Hedgehog ligand and regulating the appropriate dose-dependent response.