Deletion of Phf21b gene is known to be associated with cancer and depression. New research now indicates that timely expression of this gene plays a key role in neural stem cell differentiation and brain development
A latest research published in the journal Genes and Development on 20 March 2020, implicates role of Phf21b protein encoded by PHF21B gene in neural stem cell differentiation. In addition, deletion of Phf21b in vivo, not only inhibited neural cell differentiation but also resulted in cortical progenitor cells to undergo faster cell cycles. The current study by researchers at the Queen’s University of Belfast implicates timely expression of phf21b protein as essential for neural stem cell differentiation during cortical development1. The role of Phf21b in differentiation of neural stem cells represent a significant step in the understanding of neurogenesis in cortical cell development and will enhance our understanding of the complex process of brain development and its regulation which has been poorly understood till now with respect to the switch between proliferation and differentiation during neurogenesis.
The story of the PHF21B gene can be attributed to have started about two decades ago when in the year 2002, Real time PCR studies indicated that deletion of 22q.13 region of chromosome 22 has poor prognosis in oral cancer2. This was further confirmed a few years later in 2005 when Bergamo et al3 showed using cytogenetic analyses that deletion of this region of chromosome 22 is associated with head and neck cancers.
Almost a decade later in 2015, Bertonha and colleagues identified the PHF21B gene as a consequence of deletion of 22q.13 region4. The deletions were confirmed in a group of head and neck squamous cell carcinoma patients as well as reduced expression of PHF21B was attributed to hypermethylation confirming its role as a tumour suppressor gene. A year later in 2016, Wong et al showed association of this gene in depression as a consequence of high stress that causes reduced expression of PHF21B 5.
This study and further research on the expression analyses of phf21b in both space and time would pave way for early diagnosis and better treatment of neurological diseases such as depression, mental retardation and other brain related diseases such as Alzheimer’s and Parkinson’s.
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References:
1. Basu A, Mestres I, Sahu SK, et al 2020. Phf21b imprints the spatiotemporal epigenetic switch essential for neural stem cell differentiation. Genes & Dev. 2020. DOI: https://doi.org/10.1101/gad.333906.119
2. Reis, PP, Rogatto SR, Kowalski LP et al. Quantitative real-time PCR identifies a critical region of deletion on 22q13 related to prognosis in oral cancer. Oncogene 21: 6480-6487, 2002. DOI: https://doi.org/10.1038/sj.onc.1205864
3. Bergamo NA, da Silva Veiga LC, dos Reis PP et al. Classic and molecular cytogenetic analyses reveal chromosomal gains and losses correlated with survival in head and neck cancer patients. Clin. Cancer Res. 11: 621-631, 2005. Available online at https://clincancerres.aacrjournals.org/content/11/2/621
4. Bertonha FB, Barros Filho MdeC, Kuasne H, dos Reis PP, da Costa Prando E., Munoz JJAM, Roffe M, Hajj GNM, Kowalski LP, Rainho CA, Rogatto SR. PHF21B as a candidate tumor suppressor gene in head and neck squamous cell carcinomas. Molec. Oncol. 9: 450-462, 2015. DOI: https://doi.org/10.1016/j.molonc.2014.09.009
5. Wong M, Arcos-Burgos M, Liu S et al. The PHF21B gene is associated with major depression and modulates the stress response. Mol Psychiatry 22, 1015–1025 (2017). DOI: https://doi.org/10.1038/mp.2016.174
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