| Περίληψη: | Geminin (Gmnn) is a nuclear protein that regulates the licensing
of DNA replication, as well as cell fate decisions.1 To this end, it
is becoming increasingly evident that Geminin regulates transcrip-
tional programs associated with lineage specification. Neural crest
cells (NCCs), which originate at the dorsalmost region of the neu-
ral tube, are a transient, embryonic cell population characterized by
unusual migratory ability and developmental plasticity unique to ver-
tebrates that gives rise to a diverse cell lineage including melanocytes,
craniofacial cartilage and bone, smooth muscle, peripheral and enteric
neurons and glia. The Neural crest cell population shows a tremen-
dous potential to differentiate and contribute to almost every organ
in the adult body. In fact they are so important that they have been
called the forth germ layer2. Neural Crest Compartment can be di-
vided into four main functional cell lineages, which include the cranial
neural crest, trunk neural crest, cardiac neural crest, vagal and sacral
neural crest3. The aim of this study is to identify the gene network
directed by geminin in order to coordinate the neural crest stem cell
derivation towards mature cells.
In order to examine the role of Geminin on neural crest cells, we have
used conditional knockout mice to ablate Geminin early in the de-
veloping embryonic neural crest compartment. Specifically, we have
used mice that express the Cre recombinase under the control of the
Wnt1 gene regulatory elements (Wnt1:iCre) and the loxP system to
delete Geminin from neural crest cells. In order to dissect the molec-
ular basis of the phenotype, we have used cDNA microarray analyses,
which revealed the deregulation of genes involved in cellular lineage
specification transcription programs and epigenetic regulation. Gene
expression data mining in combination with in silico comparative anal-
yses support further our findings and suggest a key role for Geminin in
neural crest development at the transcriptional and epigenetic levels.
For the unpaired T-test we set p value threshold at 0.05. We have a
scientific interest only in genes that have a fold change greater than
the absolute value of 1.5.
Our results show that deletion of Geminin causes in embryos severe
morphological and craniofacial malformations. Embryos lacking Gem-
inin at neural crest cells die a few days before birth. Geminin acts as
a key regulatory element in neural crest stem cells during embryoge-
nesis. Geminin is associated with pathways that regulate neural crest
cell self-renew and differentiation. In other words, geminin is essen-
tial for the proper development of all the tissues that derive from the
neural crest stem cells population.
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