EPIGENETIC MODIFICATION IN FACIAL DEVELOPMENT
Main Article Content
Keywords
Epigenetic modification, Facial development, DNA methylation, Histone acetylation, Craniofacial morphogenesis
Abstract
Background: Epigenetic modifications, such as DNA methylation and histone acetylation, play a critical role in the regulation of gene expression during facial development. These changes are crucial for the proper morphogenesis of craniofacial structures, which are primarily derived from neural crest cells.
Objective: This study aimed to explore the impact of epigenetic modifications on the expression of key genes involved in craniofacial development, including MSX1, PAX9, and FGF8, using both in vitro and in vivo models.
Methods: This study investigated the role of epigenetd. Mouse neural crest cells were cultured and treated with 5-aza-2'-deoxycytidine (2 μM) to inhibic modifications in facial development, focusing on DNA methylation and histone modifications. Facial tissue samples from mouse embryos (E9.5–E12.5) and human fetal tissues were collecteit DNA methylation and Trichostatin A (0.5 μM) to increase histone acetylation. DNA methylation levels were quantified using an ELISA-based 5-methylcytosine kit, while bisulfite sequencing was used for site-specific analysis of key craniofacial genes (MSX1, PAX9, FGF8). Gene expression levels were assessed by qPCR, normalizing to GAPDH.
Results: DNA methylation was reduced significantly in treated cells, with increased expression of key genes (MSX1, PAX9, FGF8). TSA treatment led to enhanced histone acetylation, promoting higher expression of these genes. Statistical analysis confirmed significant differences (p<0.05) between treated and control groups, highlighting the impact of epigenetic changes on facial morphogenesis.
Conclusion: Epigenetic modifications, particularly through DNA methylation and histone acetylation, play a vital role in regulating the expression of genes crucial for craniofacial development. These findings provide new insights into the mechanisms of facial morphogenesis and may have implications for understanding craniofacial malformations.
References
2. Zhang J, Tian Z, Qin C, Momeni MR. The effects of exercise on epigenetic modifications: focus on DNA methylation, histone modifications and non-coding RNAs. Human Cell. 2024;37(4):887-903. doi:10.1007/s13577-024-01057-y
3. Liu S, Xu L, Kashima M, et al. Expression analysis of genes including Zfhx4 in mice and zebrafish reveals a temporospatial conserved molecular basis underlying craniofacial development. Developmental Dynamics. September 2024. doi:10.1002/dvdy.740
4. Kyriakoudi SA, Chatzi D, Dermitzakis I, et al. Genetic identity of neural crest cell differentiation in tissue and organ development. Frontiers in Bioscience-Landmark. 2024;29(7):261. doi:10.31083/j.fbl2907261
5. Trybek G, Jaroń A, Gabrysz-Trybek E, et al. Genetic factors of teeth impaction: polymorphic and haplotype variants of PAX9, MSX1, AXIN2, and IRF6 genes. International Journal of Molecular Sciences. 2023;24(18):13889. doi:10.3390/ijms241813889
6. Kumari U, Sharma RK, Keshari JR, Sinha A. Environmental exposure: effect on maternal morbidity and mortality and neonatal health. Cureus. May 2023. doi:10.7759/cureus.38548
7. Matsushita N. Dysregulated histone acetylation causes congenital diseases. Gene Reports. 2023;31:101778. doi:10.1016/j.genrep.2023.101778
8. Akintoye SO, Adisa AO, Okwuosa CU, Mupparapu M. Craniofacial disorders and dysplasias: Molecular, clinical, and management perspectives. Bone Reports. March 2024:101747. doi:10.1016/j.bonr.2024.101747
9. Strobl-Mazzulla PH, Bronner ME. Epigenetic regulation of neural crest cells. In: Elsevier eBooks. ; 2013:89-100. doi:10.1016/b978-0-12-401730-6.00005-3
10. Alamer OB, Jimenez AE, Azad TD. Single-suture craniosynostosis and the epigenome: current evidence and a review of epigenetic principles. Neurosurgical FOCUS. 2021;50(4):E10. doi:10.3171/2021.1.focus201008
11. Garland MA, Sun B, Zhang S, Reynolds K, Ji Y, Zhou CJ. Role of epigenetics and miRNAs in orofacial clefts. Birth Defects Research. 2020;112(19):1635-1659. doi:10.1002/bdr2.1802
12. Aghagoli G, Conradt E, Padbury JF, et al. Social Stress-Related epigenetic changes associated with increased heart rate variability in infants. Frontiers in Behavioral Neuroscience. 2020;13. doi:10.3389/fnbeh.2019.00294
13. Gou Y, Zhang T, Xu J. Transcription factors in craniofacial development. Current Topics in Developmental Biology/Current Topics in Developmental Biology. January 2015:377-410. doi:10.1016/bs.ctdb.2015.07.009
14. Martin DM. Epigenetic Developmental Disorders: CHARGE Syndrome, a case study. Current Genetic Medicine Reports. 2014;3(1):1-7. doi:10.1007/s40142-014-0059-1
15. Tian FY, Marsit CJ. Environmentally Induced epigenetic plasticity in development: Epigenetic toxicity and epigenetic adaptation. Current Epidemiology Reports. 2018;5(4):450-460. doi:10.1007/s40471-018-0175-7
16. Bearer EL, Mulligan BS. Epigenetic Changes Associated with Early Life Experiences: Saliva, A Biospecimen for DNA Methylation Signatures. Current Genomics. 2018;19(8):676-698. doi:10.2174/1389202919666180307150508
17. Brook AH. Multilevel complex interactions between genetic, epigenetic and environmental factors in the aetiology of anomalies of dental development. Archives of Oral Biology. 2009;54:S3-S17. doi:10.1016/j.archoralbio.2009.09.005
18. Ballestar E, Esteller M, Richardson BC. The epigenetic face of systemic lupus erythematosus. The Journal of Immunology. 2006;176(12):7143-7147. doi:10.4049/jimmunol.176.12.7143
19. Yang J, Zhu L, Pan H, et al. A BMP-controlled metabolic-epigenetic signaling cascade directs midfacial morphogenesis. Journal of Clinical Investigation. March 2024. doi:10.1172/jci165787
20. Cipriano A, Colantoni A, Calicchio A, et al. Transcriptional and epigenetic characterization of a new in vitro platform to model the formation of human pharyngeal endoderm. Genome Biology. 2024;25(1). doi:10.1186/s13059-024-03354-z
21. Bienkowska A, Raddatz G, Söhle J, et al. Development of an epigenetic clock to predict visual age progression of human skin. Frontiers in Aging. 2024;4. doi:10.3389/fragi.2023.1258183
22. DeLorenzo L, Powder KE. Epigenetics and the evolution of form: Experimental manipulation of a chromatin modification causes species‐specific changes to the craniofacial skeleton. Evolution & Development. 2023;26(1). doi:10.1111/ede.12461
23. Al-Mozey A a. a. A m., El-Salam MMA, Okasha EF a. E m., Salah EF. Comparative histological study of the role of Platelet-Rich plasma and fetal bovine serum supplemented stem cell in treatment of sciatic nerve crush injury in albino rat. Tanta Medical Journal. 2024;52(2):169-173. doi:10.4103/tmj.tmj_41_23
24. Heydari Z, Moeinvaziri F, Mirazimi SMA, et al. Alteration in DNA methylation patterns: Epigenetic signatures in gastrointestinal cancers. European Journal of Pharmacology. 2024;973:176563. doi:10.1016/j.ejphar.2024.176563
25. Lin C, Liu S, Ruan N, et al. Cleft palate induced by augmented fibroblast growth factor-9 signaling in cranial neural crest cells in mice. Stem Cells and Development. August 2024. doi:10.1089/scd.2024.0077
26. Atilano SR, Abedi S, Ianopol NV, et al. Differential Epigenetic Status and Responses to Stressors between Retinal Cybrids Cells with African versus European Mitochondrial DNA: Insights into Disease Susceptibilities. Cells. 2022;11(17):2655. doi:10.3390/cells11172655
27. Bräuer AU, Sevecke‐Rave J, Gläser A, Nahrath P, Hummel T, Witt M. Optimization of mRNA extraction from human nasal mucosa biopsies for gene expression profile analysis by qRT‐PCR. Clinical Anatomy. 2023;36(7):1001-1006. doi:10.1002/ca.24081
28. Boruah S, V VN. Comparison of the effect of simulated gastric juice on surface roughness and flexural strength of three different computer aided designing computer aided manufacturing blocks: an in vitro study. | EBSCOHost. Published July 1, 2024.
29. Shull LC, Artinger KB. Epigenetic regulation of craniofacial development and disease. Birth Defects Research. 2023;116(1). doi:10.1002/bdr2.2271
30. Wang F, Gao T, Yang X, et al. DNA methylation plays a critical role in testicular maintenance, but not in sex determination of male tilapia Oreochromis niloticus. Aquaculture. 2024;595:741455. doi:10.1016/j.aquaculture.2024.741455
31. Wójcikowska B, Chwiałkowska K, Nowak K, et al. Transcriptomic profiling reveals histone acetylation-regulated genes involved in somatic embryogenesis in Arabidopsis thaliana. BMC Genomics. 2024;25(1). doi:10.1186/s12864-024-10623-5
32. Shull LC, Artinger KB. Epigenetic regulation of craniofacial development and disease. Birth Defects Research. 2023;116(1). doi:10.1002/bdr2.2271
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Dr Abdul Aleem
BDS, MCPS ,Senior Registrar, Department of Community Dentistry , Karachi Medical and Dental College, Karachi Metropolitan University , PhD Scholar, SIOHS Jinnah Sindh Medical University
Dr Samra Bokhari
Senior Registrar, National Institute of Child Health Karachi , BDS, FCPS, M-Orth, MBA (HHCM), CHPE, PhD Scholar SIOHS Jinnah Sindh Medical University
Dr. Nauman Shirazi
Demonstrator, Karachi Medical and Dental College , Karachi Metropolitan University
Dr Tauseef Ahmed
Assistant Professor,Department of Oral Pathology , Liaquat College of Medicine and Dentistry
Dr Abdul Wajid
BDS, Lecturer,Department of Oral Medicin , Dr Isharat ul Ibad Khan Institute of Oral Health Sciences (DIKIOHS)
Dr Filza Minhas
Oral Biology, Demonstrator,Karachi Medical Dental College , Karachi Metropolitan University
Prof Dr Muhammad Khalil Khan
BDS, MPH, DPA, MCPS, PhD , Periodontology Dept. SIOHS , Director PhD Dental Sciences Program Jinnah Sindh Medical University