Pou4f2, also known as Brn-3b, is a POU homeodomain transcription factor. It plays crucial roles in multiple biological processes. In the development of retinal ganglion cells (RGCs), it acts as a key node in the gene regulatory network, regulating RGC development, axon outgrowth and pathfinding [2,4,5]. In cardiometabolic tissues, it controls genes regulating cardiometabolic function, being important for normal metabolic function and adaptive cardiac responses [1]. Genetic models like Pou4f2-GFP knock-in and Pou4f2(Cre) knock-in mice are useful tools for studying its functions [2,4].

In mice, constitutive Pou4f2-knockout (KO) leads to profound metabolic dysfunction such as hyperglycaemia and insulin resistance, highlighting its role in metabolic regulation [1]. Deletion of Pou4f2 in mice results in RGC axon defects and apoptosis, demonstrating its essentiality in RGC development [2]. In addition, male Brn-3b KO mice develop adverse cardiac remodelling and reduced cardiac function, indicating its importance in cardiac responses [1]. In colorectal cancer cells, depletion of POU4F2 suppresses metastatic phenotypes, suggesting its role as a tumor promotor through Hedgehog-mediated epithelial-mesenchymal transition [3].

In conclusion, Pou4f2 is essential for RGC development, cardiometabolic function, and has implications in cancer metastasis. Studies using KO mouse models have significantly enhanced our understanding of its functions in these biological processes and disease conditions, providing potential targets for treating metabolic, cardiovascular, and cancer-related diseases.

References:

1. Budhram-Mahadeo, Vishwanie S, Solomons, Matthew R, Mahadeo-Heads, Eeshan A O. 2021. Linking metabolic dysfunction with cardiovascular diseases: Brn-3b/POU4F2 transcription factor in cardiometabolic tissues in health and disease. In Cell death & disease, 12, 267. doi:10.1038/s41419-021-03551-9. https://pubmed.ncbi.nlm.nih.gov/33712567/

2. Zheng, Dongwang, Yang, Xiaoyan, Sheng, Donglai, Yang, Yang, Wang, Yuying. 2016. Pou4f2-GFP knock-in mouse line: A model for studying retinal ganglion cell development. In Genesis (New York, N.Y. : 2000), 54, 534-541. doi:10.1002/dvg.22960. https://pubmed.ncbi.nlm.nih.gov/27532212/

3. Guo, Kaibo, Wang, Peipei, Zhang, Leyin, Ruan, Shanming, Sun, Leitao. 2021. Transcription factor POU4F2 promotes colorectal cancer cell migration and invasion through hedgehog-mediated epithelial-mesenchymal transition. In Cancer science, 112, 4176-4186. doi:10.1111/cas.15089. https://pubmed.ncbi.nlm.nih.gov/34327778/

4. Simmons, Aaron B, Bloomsburg, Samuel J, Billingslea, Samuel A, Thomas, Marshall W, Fuerst, Peter G. 2016. Pou4f2 knock-in Cre mouse: A multifaceted genetic tool for vision researchers. In Molecular vision, 22, 705-17. doi:. https://pubmed.ncbi.nlm.nih.gov/27390513/

5. Oliveira-Valença, Viviane Medeiros, Roberts, Jacqueline Marie, Fernandes-Cerqueira, Vitória Melo, Vetter, Monica Lynn, da Silveira, Mariana Souza. 2025. POU4F2 overexpression promotes the genesis of retinal ganglion cell-like projection neurons from late progenitors. In Development (Cambridge, England), 152, . doi:10.1242/dev.204297. https://pubmed.ncbi.nlm.nih.gov/39946314/