Project Details
Projekt
Timing neural crest production by epigenetic control
Applicant
Daniela Roellig, Ph.D.
Subject Area
Developmental Neurobiology
Term
from 2012 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 215249890
The neural crest (NC) is a transient embryonic structure that emerges from the neural tube during early stages of vertebrate development. NC cells give rise to numerous derivatives like neurons and glia of the peripheral nervous system, melanocytes, cranial bone and cartilage. A complex regulatory network of transcription factors and signaling molecules drives NC formation. Unexpectedly, recent findings in the host lab suggest that epigenetic regulation by the DNA methyltransferases DNMT3a and 3b is crucial for this process. These enzymes are known to inhibit gene expression, but how they contribute to NC development is not known. Therefore, I will analyze their functional participation in NC production using loss/gain-of-function of DNMT3a/b and time-lapse imaging. Next, I plan to identify potential downstream candidates by DNMT3a/b knock-down and large-scale gene expression analysis. Finally, I will verify direct targets by performing chromatin immunoprecipitation and find possible specificity-enhancing binding partners of DNMT3a/b by mass-spectrometry. My work will show for the first time the involvement and molecular mechanism of DNA methylation in gene regulation during NC production. The results will expand the current model of NC production by clarifying how it is timed and will most likely give new insights into NC-derived diseases. More generally, it will emphasize the importance of epigenetic gene control for embryonic development.
DFG Programme
Research Fellowships
International Connection
USA
