Scube3, or signal peptide-CUB-EGF domain-containing protein 3, is a multifunctional secreted glycoprotein. It belongs to the SCUBE family and functions as a co-receptor for various growth factors, modulating signaling pathways like TGF-β, BMP, and FGF [1,2,3,4]. It is involved in numerous biological processes such as development of tissues like teeth, bones, and muscles, and is also associated with diseases including cancer and systemic lupus erythematosus [2-4,6-8]. Genetically modified mouse models have been crucial in understanding its function.

In Scube3 -/- mice, craniofacial and dental defects, reduced body size, and defective endochondral bone growth were observed due to impaired BMP-mediated chondrogenesis and osteogenesis, mirroring the human disorder caused by SCUBE3 loss-of-function [2]. In zebrafish, knockdown of scube3 specifically suppressed the expression of the myogenic marker myod1 within the lateral fast muscle precursors [4].

In conclusion, Scube3 is essential for normal development of multiple tissues, playing key roles in bone, tooth, and muscle development through its modulation of important signaling pathways. The gene knockout models in mice and zebrafish have been instrumental in revealing its role in these biological processes, and its implications in diseases such as those related to abnormal growth and differentiation of bones and teeth, as well as in certain cancers and autoimmune diseases.

References:

1. Wang, Zijie, Chen, Chuying, Zhang, Jiayi, Wu, Jiayuan, Tian, Zhihui. 2023. Epithelium-derived SCUBE3 promotes polarized odontoblastic differentiation of dental mesenchymal stem cells and pulp regeneration. In Stem cell research & therapy, 14, 130. doi:10.1186/s13287-023-03353-0. https://pubmed.ncbi.nlm.nih.gov/37189178/

2. Lin, Yuh-Charn, Niceta, Marcello, Muto, Valentina, Yang, Ruey-Bing, Tartaglia, Marco. 2020. SCUBE3 loss-of-function causes a recognizable recessive developmental disorder due to defective bone morphogenetic protein signaling. In American journal of human genetics, 108, 115-133. doi:10.1016/j.ajhg.2020.11.015. https://pubmed.ncbi.nlm.nih.gov/33308444/

3. Lin, Yuh-Charn, Sahoo, Binay K, Gau, Shiang-Shin, Yang, Ruey-Bing. 2023. The biology of SCUBE. In Journal of biomedical science, 30, 33. doi:10.1186/s12929-023-00925-3. https://pubmed.ncbi.nlm.nih.gov/37237303/

4. Tu, Cheng-Fen, Tsao, Ku-Chi, Lee, Shyh-Jye, Yang, Ruey-Bing. 2014. SCUBE3 (signal peptide-CUB-EGF domain-containing protein 3) modulates fibroblast growth factor signaling during fast muscle development. In The Journal of biological chemistry, 289, 18928-42. doi:10.1074/jbc.M114.551929. https://pubmed.ncbi.nlm.nih.gov/24849601/