Zeitliche Steuerung der Produktion von Neuralleistenzellen durch epigenetische Faktoren
Zusammenfassung der Projektergebnisse
This research work focuses on the influence of the epigenetic modifier, DNA methyl transferase (DNMT) 3A, on placode development in the early chicken embryo. The originally proposed work aimed to investigate the role of DNMT3A on neural crest development, but had since been published. Since neural crest and placodal precursors all arise from the same border territory, I refocused my research perspective to investigate the influence of DNMT3A on placodal fate. Cranial placodes are thickenings in the ectoderm that give rise to sensory organs and peripheral ganglia of the vertebrate head. At gastrula and neurula stages, placodal precursors are intermingled in the neural plate border with future neural and neural crest cells. In this research project I show that the epigenetic modifier DNMT3A is expressed in the neural plate border region and influences development of the otic placode which will contribute to the ear. DNMT3A is expressed in the presumptive otic region at gastrula through neurula stages and later in the otic placode itself. Whereas neural plate border and non-neural ectoderm markers Erni, Dlx5, Msx1 and Six1 are unaltered, DNMT3A loss of function leads to early reduction in the expression of the key otic placode specifier genes Pax2 and Gbx2 and later otic markers Sox10 and Soho1. Reduction of Gbx2 was first observed at HH7, well before loss of other otic markers. Later, this translates to significant reduction in the size of the otic vesicle. Based on these results, I propose that DNMT3A is required to activate Gbx2 expression, necessary for normal development of the ear. The study of the function of DNMT3A during placode development helps to better understand the developmental and molecular bases of hearing-loss related diseases.
Projektbezogene Publikationen (Auswahl)
- The epigenetic modifier DNMT3A is necessary for proper otic placode formation. Dev. Biol. Volume 411, Issue 2, 15 March 2016, Pages 294-300
Roellig, D.; Bronner, M.
(Siehe online unter https://doi.org/10.1016/j.ydbio.2016.01.034)
