Dmrta1, doublesex and mab-3-related transcription factor-like family A1, is a transcription factor involved in multiple biological processes. It has been implicated in regulating gene expression, with potential roles in neural development, cell proliferation, and differentiation. It may participate in various pathways, and its study can be facilitated by genetic models [2,7].

In esophageal squamous cell carcinoma (ESCC), knockdown of Dmrta1 decreased the proliferation rate of esophageal squamous carcinoma cells and increased cisplatin sensitivity, while also reducing immune escape. Mechanistically, Dmrta1 forms a positive-feedback loop with SOX2 by binding to the promoter of SOX2, promoting ESCC progression and chemoresistance [1].

In the mammalian telencephalon, Dmrta1 expression was down-regulated in Pax6 homozygous mutant rats. Overexpression of Dmrta1 induced the expression of the proneural gene Neurogenin2 and repressed Ascl1, suggesting its role in cortical neurogenesis [2].

In relation to dental fear and anxiety, a genome-wide association study found an association between Dmrta1 and the physiological arousal and avoidance sub-scales of dental fear and anxiety [3].

In a pan-cancer in-silico analysis, alteration in the copy number and expression of Dmrta1 in the chr9p22.1-21.3 locus was associated with poor survival in sarcoma datasets [4].

In the context of Nager syndrome, Sf3b4 knockdown in Xenopus embryos led to reduced expression of dmrta1 among other pan-placodal genes, which may be related to sensorineural hearing loss [5].

In yak hearts, Dmrta1 was identified as one of the key transcription factors in the cardiomyocyte module, potentially related to the yak's adaptation to high-altitude hypoxia [6].

In the telencephalon, Dmrta1 and Dmrt3 cooperatively regulate the patterning of the cortical hem structure and the production of Cajal-Retzius cells from the cortical hem during cortical development [7].

In conclusion, Dmrta1 is crucial in multiple biological processes such as cancer development, neural development, and adaptation to environmental changes. Model-based research, especially studies involving knockdown or mutation of Dmrta1, has revealed its significance in various disease conditions, including cancer and potentially in syndromes like Nager syndrome. Understanding Dmrta1's functions provides insights into disease mechanisms and may offer potential therapeutic targets.

References:

1. Zhang, Rui, Zhou, Peng, Ou, Xia, Xi, Mian, Qing, Chen. 2023. The DMRTA1-SOX2 positive feedback loop promotes progression and chemotherapy resistance of esophageal squamous cell carcinoma. In Oncology research, 31, 887-897. doi:10.32604/or.2023.030184. https://pubmed.ncbi.nlm.nih.gov/37744275/

2. Kikkawa, Takako, Obayashi, Takeshi, Takahashi, Masanori, Numayama-Tsuruta, Keiko, Osumi, Noriko. 2013. Dmrta1 regulates proneural gene expression downstream of Pax6 in the mammalian telencephalon. In Genes to cells : devoted to molecular & cellular mechanisms, 18, 636-49. doi:10.1111/gtc.12061. https://pubmed.ncbi.nlm.nih.gov/23679989/

3. Zhou, Y, McNeil, D W, Haworth, S, Marazita, M L, Shaffer, J R. 2022. Genome-wide Scan of Dental Fear and Anxiety Nominates Novel Genes. In Journal of dental research, 101, 1526-1536. doi:10.1177/00220345221105226. https://pubmed.ncbi.nlm.nih.gov/35771046/

4. Gonçalves, Paola G, Reis, Rui M, Bidinotto, Lucas T. . Significance of Chr9p22.1-p21.3 Deletion in Cancer Development: A Pan-cancer In Silico Analysis. In Anticancer research, 42, 5291-5304. doi:10.21873/anticanres.16036. https://pubmed.ncbi.nlm.nih.gov/36288884/

5. Maharana, Santosh Kumar, Saint-Jeannet, Jean-Pierre. 2021. Molecular mechanisms of hearing loss in Nager syndrome. In Developmental biology, 476, 200-208. doi:10.1016/j.ydbio.2021.04.002. https://pubmed.ncbi.nlm.nih.gov/33864777/

6. Chen, Yibo, Meng, Xiangqiong, Wan, Ruidong, Yu, Hongxian, Wei, Qing. 2023. Single-cell transcriptomic survey of cell diversity and functional changes in yak hearts at different altitude. In Proteomics, 23, e2200345. doi:10.1002/pmic.202200345. https://pubmed.ncbi.nlm.nih.gov/36739517/

7. Kikkawa, Takako, Sakayori, Nobuyuki, Yuuki, Hayato, Kiyonari, Hiroshi, Osumi, Noriko. 2020. Dmrt genes participate in the development of Cajal-Retzius cells derived from the cortical hem in the telencephalon. In Developmental dynamics : an official publication of the American Association of Anatomists, 249, 698-710. doi:10.1002/dvdy.156. https://pubmed.ncbi.nlm.nih.gov/32012381/