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Brownell, I., Guevara, E., Bai, C. B., Loomis, C. A. & Joyner, A. L. Nerve-derived sonic hedgehog defines a niche for hair follicle stem cells capable of becoming epidermal stem cells. Cell Stem Cell 8, 552–565 (2011). Wu F, Zhang C, Zhao C, Wu H, Teng Z, Jiang T. Prostaglandin E1 Inhibits GLI2 amplification-associated activation of the hedgehog pathway and drug refractory tumor growth. Cancer Res. 2020;80(13):2818–32. Rohatgi, R. & Scott, M. P. Patching the gaps in Hedgehog signalling. Nat. Cell Biol. 9, 1005–1009 (2007).

Garden birds like robins, blue tits and finches will benefit greatly from the B&M bird feeding station, - particularly in the nesting season and in colder months when the ground is frozen and food is harder to come by and birds begin to rely on the provision of bird seed and other nutrients. Rohatgi, R., Milenkovic, L. & Scott, M. P. Patched1 regulates hedgehog signaling at the primary cilium. Science 317, 372–376 (2007). Taylor, F. R. et al. Enhanced potency of human Sonic hedgehog by hydrophobic modification. Biochemistry 40, 4359–4371 (2001). Furthermore, we demonstrated that Smo agonist SAG stimulated Shh activitiy could be suppressed by 0025A using similar approaches as Shh-CM (Fig. 8b–d). In addition, we also detect the expression of Ptch1, which is another target gene of Hh signaling pathway [ 39], and found that 0025A could dose-dependently inhibit the mRNA level of Ptch1 induced by 20% Shh-CM (Additional file 1: Fig. S1). Taken together, the above results indicate that 0025A can act as a potent inhibitor and dose-dependently inhibit target gene expression of the Shh signaling pathway. 0025A inhibits hair regrowth and hair follicle morphogenesis The best ways of assisting hedgehogs are by helping them avoid man-made hazards and providing them with suitable places to nest, especially in the winter. Slug PelletsSkoda AM, Simovic D, Karin V, Kardum V, Vranic S, Serman L. The role of the Hedgehog signaling pathway in cancer: a comprehensive review. Bosn J Basic Med Sci. 2018;18(1):8–20. Wu VM, Chen SC, Arkin MR, Reiter JF. Small molecule inhibitors of Smoothened ciliary localization and ciliogenesis. Proc Natl Acad Sci USA. 2012;109(34):13644–9. A large plastic box is another option for the house, but make sure to cut an entrance and plenty of breathing holes. Camouflage the box in the same way, with logs and leaf litter. This should only be done when you are sure there are no hedgehog occupants. There are two opportunities to clean a hedgehog house each year. The first is in April, when a hedgehog will vacate the house after coming out of hibernation. Findakly, S. et al. Sterol and oxysterol synthases near the ciliary base activate the Hedgehog pathway. J. Cell Biol. https://doi.org/10.1083/jcb.202002026 (2021).

The animal studies were performed as previously described [ 30]. Briefly, female C57BL/6 mice (aged 7 to 8 weeks) were shaved dorsal hair and the bottom half of shaved area was depilated with Nair for 2 min. After depilation, the mice were topically treated with 30 μL of 5 mM 0025A dissolved in a vehicle of 95% acetone/5% DMSO or the vehicle once daily for 14 consecutive days and observed the pigment formation and hair regrowth. During the experimental procedures, the mice were anesthetized by 3% isoflurane and the studies were performed according to the ethical principles of animal welfare of Beijing Institute of Neurosurgery. Statistical analysisLee, J. D. & Treisman, J. E. Sightless has homology to transmembrane acyltransferases and is required to generate active Hedgehog protein. Curr. Biol. 11, 1147–1152 (2001). Ekker, S. C. et al. Patterning activities of vertebrate hedgehog proteins in the developing eye and brain. Curr. Biol. 5, 944–955 (1995). Qian, H. et al. Structural basis of low-pH-dependent lysosomal cholesterol egress by NPC1 and NPC2. Cell 182, 98–111 e118 (2020). Johnston, J. J. et al. Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations. Am. J. Hum. Genet. 76, 609–622 (2005). Lee MJ, Hatton BA, Villavicencio EH, Khanna PC, Friedman SD, Ditzler S, et al. Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model. Proc Natl Acad Sci USA. 2012;109(20):7859–64.