Shh, short for Sonic hedgehog, is a member of the hedgehog gene families. It plays a critical role in the embryonic development of various tissues and organs. The Shh signaling pathway is essential in processes like cell division, cellular differentiation, and maintaining neuronal integrity [2,3,4]. It is involved in multiple biological pathways, with its dysregulation linked to various diseases, making genetic models valuable for its study.

Mouse embryos lacking Shh or its essential signal transduction components display cochlear agenesis, indicating Shh's role in cochlear duct morphogenesis [6]. In the context of medulloblastoma, the SHH group is characterized by constitutive activation of the SHH signaling pathway, often due to mutations in PTCH1 or other downstream pathway mutations, and SHH inhibitors are being explored for treatment [1]. In adamantinomatous craniopharyngioma, inhibiting the SHH pathway with vismodegib led to a significant reduction in median survival and increased tumour cell proliferation, showing a protumourigenic effect [5].

In conclusion, Shh is crucial for embryonic development, especially in the formation of organs like the cochlea. Studies using gene knockout mouse models have revealed its role in disease conditions such as medulloblastoma and adamantinomatous craniopharyngioma. Understanding Shh's functions through these models provides insights into disease mechanisms and potential therapeutic strategies for related diseases.

References:

1. Samkari, Ayman, White, Jason, Packer, Roger. 2015. SHH inhibitors for the treatment of medulloblastoma. In Expert review of neurotherapeutics, 15, 763-70. doi:10.1586/14737175.2015.1052796. https://pubmed.ncbi.nlm.nih.gov/26027634/

2. Wang, Xiang-Zhi, Zhang, Hang-Hu, Qian, Yu-Ling, Tang, Lan-Fang. . Sonic hedgehog (Shh) and CC chemokine ligand 2 signaling pathways in asthma. In Journal of the Chinese Medical Association : JCMA, 82, 343-350. doi:10.1097/JCMA.0000000000000094. https://pubmed.ncbi.nlm.nih.gov/31058710/

3. Prajapati, Aradhana, Mehan, Sidharth, Khan, Zuber. 2023. The role of Smo-Shh/Gli signaling activation in the prevention of neurological and ageing disorders. In Biogerontology, 24, 493-531. doi:10.1007/s10522-023-10034-1. https://pubmed.ncbi.nlm.nih.gov/37097427/

4. Li, Xiaoying, Li, Yunxiao, Li, Shuanqing, Yang, Ciqing, Lin, Juntang. 2020. The role of Shh signalling pathway in central nervous system development and related diseases. In Cell biochemistry and function, 39, 180-189. doi:10.1002/cbf.3582. https://pubmed.ncbi.nlm.nih.gov/32840890/

5. Carreno, G, Boult, J K R, Apps, J, Robinson, S P, Martinez-Barbera, J P. . SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma. In Endocrine-related cancer, 26, 355-366. doi:10.1530/ERC-18-0538. https://pubmed.ncbi.nlm.nih.gov/30645190/

6. Muthu, Victor, Rohacek, Alex M, Yao, Yao, Peterson, Kevin A, Epstein, Douglas J. 2019. Genomic architecture of Shh-dependent cochlear morphogenesis. In Development (Cambridge, England), 146, . doi:10.1242/dev.181339. https://pubmed.ncbi.nlm.nih.gov/31488567/