Understanding Sonic hedgehog (Shh) expression and its distribution in common house gecko (Hemidactylus platyurus) tail regeneration

Maytia Pratiwisitha; Ria Margiana; Mohamad Sadikin; Ahmad Aulia Jusuf

doi:10.31893/multiscience.2025370

Keywords:

regenerative medicine

Abstract

Mammals, especially humans, have limited regenerative abilities compared to lower organisms. The common house gecko (Hemidactylus platyurus) exhibits high regenerative capacity and closer evolutionary relationship to mammals than other highly regenerative species. Observing the regeneration process in house gecko reveals insights into the biological mechanisms underlying tissue regeneration after injury. Sonic hedgehog (Shh) pathway is essential for intercellular communication during development and regeneration. In this study, Shh expression and its distribution during the tail regeneration in the common house gecko (Hemidactylus platyurus) were examined to understand the molecular mechanisms regulating regeneration. A total of 28 house geckos were divided into 7 groups based on sampling time. Autotomy procedures were conducted for all groups. The tails were allowed to regenerate, measured using graph paper, and cut to be analyzed. Hematoxylin-eosin and immunohistochemical staining using anti-Shh primary antibody were conducted to observe the microscopic structure and Shh expression. Statistical analyses were conducted to analyze the obtained data. Tail elongation was observed throughout the regeneration process. Shh expression is evident in both original and regenerated tails, commencing on day 1 post autotomy, peaking on day 14, stabilizing until day 21, and gradually decreasing by day 30. Statistical analysis showed significant differences on tail length measurement and Shh expression between groups (p < 0.001). The results showed strong positive correlation between Shh expression and regenerated tail length from day 1 to day 14 (R=0.818; p<0.001). Additionally, strong negative correlation was observed between Shh expression and regenerated tail length from day 21 to day 30 (R=-0.852; p<0.001). Shh protein is detected in a variety of cell types within both original and regenerated tail tissues. It plays critical role in maintaining tissue homeostasis in adult tissues and facilitating the proliferation, migration, and differentiation of blastema cells in response to injury.
References
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

How to cite

Pratiwisitha, M., Margiana, R., Sadikin, M., & Jusuf, A. A. (2025). Understanding Sonic hedgehog (Shh) expression and its distribution in common house gecko (Hemidactylus platyurus) tail regeneration. Multidisciplinary Science Journal, 7(9), 2025370. https://doi.org/10.31893/multiscience.2025370

[1] Alibardi, L. (2010). Morphological and cellular aspects of tail and limb regeneration in lizards: A model system with implications for tissue regeneration in mammals. In H. W. Korf, F. Beck, F. Clasca, M. Frotscher, D. Haines, N. Hirokawa, Z. Kmiec, E. Marani, R. Putz, & J. P. Timmermans (Eds.), Advances in anatomy, embryology and cell biology. Springer. http://www.springer.com/series/102

[2] Bangs, F., & Anderson, K. V. (2017). Primary Cilia and Mammalian Hedgehog Signaling. Cold Spring Harbor Perspectives in Biology, 9(5). https://doi.org/10.1101/cshperspect.a028175

[3] Barresi, M. J. F., & Gilbert, S. F. (2020). Developmental Biology (12th ed.). Oxford University Press.

[4] Belgacem, Y. H., Hamilton, A. M., Shim, S., Spencer, K. A., & Borodinsky, L. N. (2016). The many hats of Sonic hedgehog signaling in nervous system development and disease. In Journal of Developmental Biology (Vol. 4, Issue 4). MDPI Multidisciplinary Digital Publishing Institute. https://doi.org/10.3390/jdb4040035

[5] Carballo, G. B., Honorato, J. R., De Lopes, G. P. F., & Spohr, T. C. L. D. S. E. (2018). A highlight on Sonic hedgehog pathway. In Cell Communication and Signaling (Vol. 16, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s12964-018-0220-7

[6] Choudhry, Z., Rikani, A. A., Choudhry, A. M., Tariq, S., Zakaria, F., Asghar, M. W., Sarfraz, M. K., Haider, K., Shafiq, A. A., & Mobassarah, N. J. (2014). Sonic hedgehog signalling pathway: a complex network. Annals of Neurosciences, 21(1). https://doi.org/10.5214/ans.0972.7531.210109

[7] Dzobo, K., Thomford, N. E., Senthebane, D. A., Shipanga, H., Rowe, A., Dandara, C., Pillay, M., & Motaung, K. S. C. M. (2018). Advances in Regenerative Medicine and Tissue Engineering: Innovation and Transformation of Medicine. Stem Cells International, 2018, 1–24. https://doi.org/10.1155/2018/2495848

[8] Frech, S., Forsthuber, A., Korosec, A., Lipp, K., Kozumov, V., & Lichtenberger, B. M. (2022). Hedgehog Signaling in Papillary Fibroblasts Is Essential for Hair Follicle Regeneration during Wound Healing. The Journal of Investigative Dermatology, 142(6), 1737-1748.e5. https://doi.org/10.1016/j.jid.2021.11.026

[9] Goldman, J. A., & Poss, K. D. (2020). Gene regulatory programmes of tissue regeneration. In Nature Reviews Genetics (Vol. 21, Issue 9, pp. 511–525). Nature Research. https://doi.org/10.1038/s41576-020-0239-7

[10] Kyung, D. S., Lee, E., Chae, S., Son, Y., Moon, Y.-J., Hwang, D., Kim, J. K., Lee, Y.-H., & Seong, J. K. (2024). Single-cell transcriptomic analysis reveals dynamic activation of cellular signaling pathways regulating beige adipogenesis. Experimental & Molecular Medicine, 56(10), 2309–2322. https://doi.org/10.1038/s12276-024-01252-9

[11] Lau, C. I., Yánez, D. C., Papaioannou, E., Ross, S., & Crompton, T. (2022). Sonic Hedgehog signalling in the regulation of barrier tissue homeostasis and inflammation. FEBS Journal, 289(24), 8050–8061. https://doi.org/10.1111/febs.16222

[12] Lozito, T. P., & Tuan, R. S. (2017). Lizard tail regeneration as an instructive model of enhanced healing capabilities in an adult amniote. Connective Tissue Research, 58(2), 145–154. https://doi.org/10.1080/03008207.2016.1215444

[13] Lozito, T. P., Londono, R., Sun, A. X., & Hudnall, M. L. (2021). Introducing dorsoventral patterning in adult regenerating lizard tails with gene-edited embryonic neural stem cells. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-26321-9

[14] Martinez, J. A., Kobayashi, M., Krishnan, A., Webber, C., Christie, K., Guo, G. F., Singh, V., & Zochodne, D. W. (2015). Intrinsic facilitation of adult peripheral nerve regeneration by the Sonic hedgehog morphogen. Experimental Neurology, 271, 493–505. https://doi.org/10.1016/j.expneurol.2015.07.018

[15] Mastrangelo, E., & Milani, M. (2018). Role and inhibition of GLI1 protein in cancer. Lung Cancer (Auckland, N.Z.), 9, 35–43. https://doi.org/10.2147/LCTT.S124483

[16] Moradi, M., Hood, B., Moradi, M., & Atala, A. (2015). The potential role of regenerative medicine in the man-agement of traumatic patients. Journal of Injury & Violence Research, 7(1), 27–35. https://doi.org/10.5249/jivr.v7i1.704

[17] Nagumantri, S. P., Banu, S., & Idris, M. M. (2021). Transcriptomic and proteomic analysis of Hemidactylus frenatus during initial stages of tail regeneration. Scientific Reports, 11(1), 3675. https://doi.org/10.1038/s41598-021-83283-0

[18] Ninov, N., & Yun, M. H. (2015). Current advances in tissue repair and regeneration: the future is bright. Regeneration, 2(2), 84–91. https://doi.org/10.1002/reg2.30

[19] Novianti, T., Juniantito, V., Jusuf, A. A., Arida, E. A., Jusman, S. W. A., & Sadikin, M. (2019). Expression and role of HIF-1α and HIF-2α in tissue regeneration: a study of hypoxia in house gecko tail regeneration. Organogenesis, 15(3), 69–84. https://doi.org/10.1080/15476278.2019.1644889

[20] Piccioni, A., Gaetani, E., Neri, V., Gatto, I., Palladino, M., Silver, M., Smith, R. C., Giarretta, I., Pola, E., Hlatky, L., & Pola, R. (2014). Sonic hedgehog therapy in a mouse model of age-associated impairment of skeletal muscle regeneration. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 69(3), 245–252. https://doi.org/10.1093/gerona/glt076

[21] Sigafoos, A. N., Paradise, B. D., & Fernandez-Zapico, M. E. (2021). Hedgehog/GLI Signaling Pathway: Transduction, Regulation, and Implications for Disease. Cancers, 13(14). https://doi.org/10.3390/cancers13143410

[22] Straface, G., Aprahamian, T., Flex, A., Gaetani, E., Biscetti, F., Smith, R. C., Pecorini, G., Pola, E., Angelini, F., Stigliano, E., Castellot Jr., J. J., Losordo, D. W., & Pola, R. (2009). Sonic hedgehog regulates angiogenesis and myogenesis during post‐natal skeletal muscle regeneration. Journal of Cellular and Molecular Medicine, 13(8b), 2424–2435. https://doi.org/10.1111/j.1582-4934.2008.00440.x

[23] Vonk, A. C., Zhao, X., Pan, Z., Hudnall, M. L., Oakes, C. G., Lopez, G. A., Hasel-Kolossa, S. C., Kuncz, A. W. C., Sengelmann, S. B., Gamble, D. J., & Lozito, T. P. (2023). Single-cell analysis of lizard blastema fibroblasts reveals phagocyte-dependent activation of Hedgehog-responsive chondrogenesis. Nature Communications, 14(1), 4489. https://doi.org/10.1038/s41467-023-40206-z

Abstract

References

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