POGZ, the pogo transposable element-derived zinc finger protein, is significantly associated with neurodevelopmental processes. It plays a role in transcriptional regulation, maintaining mouse embryonic stem cells (ESCs) and is involved in pathways related to DNA repair, neural differentiation, and suppressing metastasis in triple-negative breast cancer [1,2,5]. Genetic models, such as KO mouse models, are valuable for studying its functions.

In KO mouse models, Pogz haploinsufficiency (Pogz + /delta) leads to developmental delay, impaired intellectual abilities, hyperactive behavior, and a compromised humoral immune response, recapitulating White Sutton syndrome (WHSUS) features. In vivo CRISPR inactivation of Pogz is embryonically lethal [2]. In human embryonic stem cells, loss of POGZ reduces neural stem cell proliferation, affects the generation of intermediate progenitor cells and early-born neurons, and perturbs neuronal migration. It also leads to a more simplified dendritic architecture in cortical-like excitatory neurons [7].

In conclusion, POGZ is crucial for maintaining ESC identity, regulating neural differentiation, and promoting homology-directed DNA repair. The study of POGZ through KO/CKO mouse models has provided insights into neurodevelopmental disorders like autism spectrum disorder, intellectual disability, and White Sutton syndrome, as well as its role in cancer metastasis [1,2,3,4,6,7,8].

References:

1. Sun, Xiaoyun, Zhang, Tianzhe, Tong, Bei, Jiang, Wei, Sun, Yuhua. 2023. POGZ suppresses 2C transcriptional program and retrotransposable elements. In Cell reports, 42, 112867. doi:10.1016/j.celrep.2023.112867. https://pubmed.ncbi.nlm.nih.gov/37494184/

2. Heath, John, Cheyou, Estelle Simo, Findlay, Steven, Maréchal, Alexandre, Orthwein, Alexandre. 2021. POGZ promotes homology-directed DNA repair in an HP1-dependent manner. In EMBO reports, 23, e51041. doi:10.15252/embr.202051041. https://pubmed.ncbi.nlm.nih.gov/34758190/

3. Ferretti, Alessandro, Barresi, Sabina, Trivisano, Marina, Tartaglia, Marco, Specchio, Nicola. 2019. POGZ-related epilepsy: Case report and review of the literature. In American journal of medical genetics. Part A, 179, 1631-1636. doi:10.1002/ajmg.a.61206. https://pubmed.ncbi.nlm.nih.gov/31136090/

4. Zhao, Wenjing, Quan, Yingting, Wu, Huidan, Guo, Hui, Xia, Kun. 2019. POGZ de novo missense variants in neuropsychiatric disorders. In Molecular genetics & genomic medicine, 7, e900. doi:10.1002/mgg3.900. https://pubmed.ncbi.nlm.nih.gov/31347273/

5. Heath, John, Mirabelli, Caitlynn, Annis, Matthew G, Orthwein, Alexandre, Ursini-Siegel, Josie. . The Neurodevelopmental Protein POGZ Suppresses Metastasis in Triple-Negative Breast Cancer by Attenuating TGFβ Signaling. In Cancer research, 84, 3743-3760. doi:10.1158/0008-5472.CAN-23-3887. https://pubmed.ncbi.nlm.nih.gov/39137399/

6. Nagy, Dóra, Verheyen, Sarah, Wigby, Kristen M, Duba, Hans-Christoph, Weis, Denisa. 2022. Genotype-Phenotype Comparison in POGZ-Related Neurodevelopmental Disorders by Using Clinical Scoring. In Genes, 13, . doi:10.3390/genes13010154. https://pubmed.ncbi.nlm.nih.gov/35052493/

7. Deng, Lu, Mojica-Perez, Sandra P, Azaria, Ruth D, Parent, Jack M, Niu, Wei. 2022. Loss of POGZ alters neural differentiation of human embryonic stem cells. In Molecular and cellular neurosciences, 120, 103727. doi:10.1016/j.mcn.2022.103727. https://pubmed.ncbi.nlm.nih.gov/35367590/

8. Sun, Xiaoyun, Cheng, Linxi, Sun, Yuhua. 2022. Autism-associated protein POGZ controls ESCs and ESC neural induction by association with esBAF. In Molecular autism, 13, 24. doi:10.1186/s13229-022-00502-9. https://pubmed.ncbi.nlm.nih.gov/35650610/