title: Geminin regulates cortical progenitor proliferation and differentiation.
abstract: During cortical development, coordination of proliferation and differentiation ensures the timely generation of different neural progenitor lineages that will give rise to mature neurons and glia. Geminin is an inhibitor of DNA replication and it has been proposed to regulate cell proliferation and fate determination during neurogenesis via interactions with transcription factors and chromatin remodeling complexes. To investigate the in vivo role of Geminin in the maintenance and differentiation of cortical neural progenitors, we have generated mice that lack Geminin expression in the developing cortex. Our results show that loss of Geminin leads to the expansion of neural progenitor cells located at the ventricular and subventricular zones of the developing cortex. Early cortical progenitors lacking Geminin exhibit a longer S-phase and a reduced ability to generate early born neurons, consistent with a preference on self-renewing divisions. Overexpression of Geminin in progenitor cells of the cortex reduces the number of neural progenitor cells, promotes cell cycle exit and subsequent neuronal differentiation. Our study suggests that Geminin has an important role during cortical development in regulating progenitor number and ultimately neuron generation.
authors.affiliation: Department of Physiology, Medical School, University of Patras, Patras, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Spella
authors.forename: Christina
authors.initials: C
authors.lastname: Kyrousi
authors.forename: Eva
authors.initials: E
authors.lastname: Kritikou
authors.forename: Athanasia
authors.initials: A
authors.lastname: Stathopoulou
authors.forename: François
authors.initials: F
authors.lastname: Guillemot
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kioussis
authors.forename: Vassilis
authors.initials: V
authors.lastname: Pachnis
authors.forename: Zoi
authors.initials: Z
authors.lastname: Lygerou
authors.forename: Stavros
authors.initials: S
authors.lastname: Taraviras
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D064248:Geminin; D055786:Gene Knockout Techniques; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology; D009562:Nissl Bodies / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D011247:Pregnancy; D012097:Repressor Proteins / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C491198:Eomes protein, mouse; D005136:Eye Proteins; D064248:Geminin; C577997:Gmnn protein, mouse; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D020825:T-Box Domain Proteins