Participación del Factor Silenciador Neuronal Restrictivo - Tesis ...

ABSTRACT
The RE-1 silencer of transcription/neural restrictive silencer factor
(REST/NRSF) was initially identified as a repressor of neuronal genes
containing a 23 base pair conserved motif sequence known as RE-1/NRSE. The
expression pattern of the mRNA encoding REST/NRSF and an extensive
molecular characterization of its function, led to the view of REST/NRSF as a
factor that silences neuronal genes in non-neuronal cell types and immature
neuronal precursors. Recently it has been shown that REST/NRSF plays distinct
roles in the transit of embryonic stem cells to differentiated neurons, and has
also been identified as a tumor suppressor gene, which is deleted in human
neoplasias. Homozygous deletion of the REST/NRSF gene is lethal for mice
around embryonic day 10. Examination of these embryos reveals derepression
of some neuronal genes in non-neural tissues. Conversely, gain of function of
REST/NRSF in developing chick spinal neurons results in repression of the
expression of some neuronal genes and defects in axon navigation. In contrast,
in Xenopus laevis embryos the interference with XREST/NRSF function from
early stages of development does not lead to early lethality and results in
repression of neuronal genes at late neurula stage and in the expansion of
neural tissue. These results contrast with the body of knowledge that emerged
from molecular studies and indicates that XREST/NRSF function is necessary
for the expression of neuronal genes. Moreover, these data along with the
observed in mouse embryos and in neural stem cells, suggest that REST/NRSF
function could be required at early stages of neural development.
In this thesis we studied the role of XREST/NRSF during Xenopus
development, from the establishment of neuroectoderm to the neuronal
differentiation. We find that impairment of XREST/NRSF function in Xenopus
embryos from late blastula stage leads to the perturbation of neural tube, cranial
ganglia and eye development. The origin of these defects is the abnormal
patterning of the ectoderm during gastrulation and early neurulae. In Xenopus
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