The role of geminin in neural crest stem cells, a functional approach through bioinformatics analyses

• Κύριος συγγραφέας: Κανελλάκης, Νικόλαος Ι.
• Άλλοι συγγραφείς: Ταραβήρας, Σταύρος
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2015
• Θέματα: Neural crest; Geminin; Stem cells; Microarrays; Νευρική ακρολοφία; Βλαστοκύτταρα; 573.853 84

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.