Tbx20, a member of the Tbx1 subfamily of T-box-containing genes, is crucial for cardiovascular development, homeostasis, and cardiac remodeling in response to pathophysiological stresses [1]. It is involved in multiple cardiogenic cell lineages and regulates transcriptional networks during cardiac development. Additionally, it has been linked to angiogenesis through the PROK2-PROKR1 pathway [5]. Genetic models, such as gene-knockout models, are valuable for studying its functions.

In cardiac development, disrupting the Tbx20-TLE interaction in a mouse model impaired cardiac looping and chamber formation, with misexpression of retinoic acid pathway and cardiac progenitor genes [3]. Loss-of-function TBX20 variants were found in families with left ventricular non-compaction cardiomyopathy (LVNC), strengthening the association between TBX20 and LVNC [4]. In colorectal cancer, down-regulation of TBX20 with promoter hypermethylation was observed in early-stage tissues, and it suppressed cell proliferation and tumor growth by impairing non-homologous DNA end-joining (NHEJ)-mediated double-stranded break repair [2].

In conclusion, Tbx20 plays essential roles in cardiovascular development, angiogenesis, and tumor suppression. Mouse models with disrupted Tbx20 functions have revealed its significance in cardiac morphogenesis and in conditions like LVNC. Understanding Tbx20 provides insights into the mechanisms of cardiovascular diseases and cancer, potentially offering new therapeutic targets.

References:

1. Chen, Yuwen, Xiao, Deyong, Zhang, Lu, Li, Bai-Yan, Liu, Ying. 2021. The Role of Tbx20 in Cardiovascular Development and Function. In Frontiers in cell and developmental biology, 9, 638542. doi:10.3389/fcell.2021.638542. https://pubmed.ncbi.nlm.nih.gov/33585493/

2. Luo, Jie, Chen, Jie-Wei, Zhou, Jie, Xie, Dan, Wang, Feng-Wei. 2022. TBX20 inhibits colorectal cancer tumorigenesis by impairing NHEJ-mediated DNA repair. In Cancer science, 113, 2008-2021. doi:10.1111/cas.15348. https://pubmed.ncbi.nlm.nih.gov/35348274/

3. Edwards, Whitney, Bussey, Olivia K, Conlon, Frank L. 2023. The Tbx20-TLE interaction is essential for the maintenance of the second heart field. In Development (Cambridge, England), 150, . doi:10.1242/dev.201677. https://pubmed.ncbi.nlm.nih.gov/37756602/

4. Chang, Yuchen, Wacker, Julie, Ingles, Jodie, Weintraub, Robert G, Bagnall, Richard D. 2024. TBX20 loss-of-function variants in families with left ventricular non-compaction cardiomyopathy. In Journal of medical genetics, 61, 171-175. doi:10.1136/jmg-2023-109455. https://pubmed.ncbi.nlm.nih.gov/37657916/

5. Meng, Shu, Gu, Qilin, Yang, Xiaojie, Cooke, John P, Fang, Longhou. . TBX20 Regulates Angiogenesis Through the Prokineticin 2-Prokineticin Receptor 1 Pathway. In Circulation, 138, 913-928. doi:10.1161/CIRCULATIONAHA.118.033939. https://pubmed.ncbi.nlm.nih.gov/29545372/