Msx2, also known as muscle segment homeobox 2, is a transcription factor with significant importance in multiple biological processes. It is involved in various pathways such as those related to cell fate decisions, stem cell maintenance, and tissue development. Genetic models, especially KO/CKO mouse models, have been crucial in understanding its functions [1,2,3,4,5,6,7].

In placental development, MSX2 depletion in human trophoblast stem cells activates the syncytiotrophoblast transcriptional program, suggesting it safeguards trophoblast identity and prevents premature syncytiotrophoblast differentiation [3]. In oral squamous cell carcinomas, MSX2 downregulation is associated with unfavorable outcomes, and its overexpression represses cancer stem cell phenotypes via SOX2 degradation [4]. In osteosarcoma cells, overexpression of MSX2 inhibits cell growth and migration by repressing SOX2 [5]. In osteoporosis, miR-151b inhibits osteoblast differentiation through downregulating Msx2 [6]. In wound-induced hair follicle neogenesis, Msx2 expression in the epidermis is required for the process, and its absence in germline and epithelial-specific Msx2 mutant mice abrogates WIHN [7].

In summary, Msx2 plays essential roles in cell fate determination, tissue development, and disease processes. Studies using KO/CKO mouse models have revealed its significance in placental development, oral and bone-related cancers, osteoporosis, and wound-induced hair follicle neogenesis, providing valuable insights into the underlying molecular mechanisms and potential therapeutic targets.

References:

1. Babajko, Sylvie, de La Dure-Molla, Muriel, Jedeon, Katia, Berdal, Ariane. 2015. MSX2 in ameloblast cell fate and activity. In Frontiers in physiology, 5, 510. doi:10.3389/fphys.2014.00510. https://pubmed.ncbi.nlm.nih.gov/25601840/

2. Ruspita, Intan, Das, Pragnya, Miyoshi, Keiko, Snead, Malcolm L, Bei, Marianna. 2023. Enam expression is regulated by Msx2. In Developmental dynamics : an official publication of the American Association of Anatomists, 252, 1292-1302. doi:10.1002/dvdy.598. https://pubmed.ncbi.nlm.nih.gov/37191055/

3. Hornbachner, Ruth, Lackner, Andreas, Papuchova, Henrieta, Mechtler, Karl, Latos, Paulina A. . MSX2 safeguards syncytiotrophoblast fate of human trophoblast stem cells. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2105130118. https://pubmed.ncbi.nlm.nih.gov/34507999/

4. Keyimu, Reziwan, Tuerdi, Maimaitituxun, Zhao, Zhihe. 2021. MSX2 represses tumor stem cell phenotypes within oral squamous cell carcinomas via SOX2 degradation. In Experimental biology and medicine (Maywood, N.J.), 246, 2660-2670. doi:10.1177/15353702211041029. https://pubmed.ncbi.nlm.nih.gov/34435915/

5. Wu, Yue, Jin, Yi, Yamamoto, Norio, Tsuchiya, Hiroyuki, Yang, Zhijun. 2021. MSX2 inhibits the growth and migration of osteosarcoma cells by repressing SOX2. In American journal of translational research, 13, 5851-5865. doi:. https://pubmed.ncbi.nlm.nih.gov/34306330/

6. Liu, Fuan, Liang, Yunbang, Lin, Xiaoyi. 2021. MiR-151b inhibits osteoblast differentiation via downregulating Msx2. In Connective tissue research, 63, 112-123. doi:10.1080/03008207.2021.1882442. https://pubmed.ncbi.nlm.nih.gov/33691558/

7. Hughes, Michael W, Jiang, Ting-Xin, Plikus, Maksim V, Widelitz, Randall B, Chuong, Cheng-Ming. 2018. Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis. In The Journal of investigative dermatology, 138, 2041-2050. doi:10.1016/j.jid.2018.02.043. https://pubmed.ncbi.nlm.nih.gov/29577917/