Transcriptional Elongation is Important for Neural Crest Development

Hatch, Victoria (2013) Transcriptional Elongation is Important for Neural Crest Development. Doctoral thesis, University of East Anglia.

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Neural crest cells are a multipotent cell population, which migrate
from the dorsal neural tube in early vertebrate development throughout
the embryo to form a variety of cell types including pigment cells, craniofacial
cartilage and sensory neurons [1, 2]. Here I show that the small
molecule compound leflunomide is able to inhibit neural crest
specification genes. Leflunomide exerts its actions by inhibiting
pyrimidine synthesis and therefore RNA transcription [4]. Neural crest
genes are thought to be actively transcribed and like many embryonic
stem cell genes may undergo an increased level of transcriptional
pausing and subsequent elongation rendering them more sensitive to the
effect of leflunomide [3, 5]. I have gone on to show that components of
the transcriptional elongation regulatory machinery, Cdk9 and CyclinT1 of
the P-TEFb complex are also able to regulate neural crest specification.
In particular the expression of the protooncogene c-Myc and c-Myc
responsive genes are affected. c-Myc has been previously implicated in
embryonic stem cell transcriptional elongation and also is well
characterised to play a role in neural crest specification [6]. We postulate
that regulation of c-Myc expression at the level of transcriptional
elongation is important for the correct temporal and spatial development
of the neural crest.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Users 2259 not found.
Date Deposited: 12 Mar 2014 09:24
Last Modified: 12 Mar 2014 09:24

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