title: Neural development is dependent on the function of specificity protein 2 in cell cycle progression.
abstract: Faithful progression through the cell cycle is crucial to the maintenance and developmental potential of stem cells. Here, we demonstrate that neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs) employ a zinc-finger transcription factor specificity protein 2 (Sp2) as a cell cycle regulator in two temporally and spatially distinct progenitor domains. Differential conditional deletion of Sp2 in early embryonic cerebral cortical progenitors, and perinatal olfactory bulb progenitors disrupted transitions through G1, G2 and M phases, whereas DNA synthesis appeared intact. Cell-autonomous function of Sp2 was identified by deletion of Sp2 using mosaic analysis with double markers, which clearly established that conditional Sp2-null NSCs and NPCs are M phase arrested in vivo. Importantly, conditional deletion of Sp2 led to a decline in the generation of NPCs and neurons in the developing and postnatal brains. Our findings implicate Sp2-dependent mechanisms as novel regulators of cell cycle progression, the absence of which disrupts neurogenesis in the embryonic and postnatal brain.
authors.affiliation: Department of Molecular Biomedical Sciences and Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607,  USA.
authors.forename: Huixuan
authors.initials: H
authors.lastname: Liang
authors.forename: Guanxi
authors.initials: G
authors.lastname: Xiao
authors.forename: Haifeng
authors.initials: H
authors.lastname: Yin
authors.forename: Simon
authors.initials: S
authors.lastname: Hippenmeyer
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Horowitz
authors.forename: H Troy
authors.initials: HT
authors.lastname: Ghashghaei
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002452:Cell Count; D002453:Cell Cycle; D049109:Cell Proliferation; D003433:Crosses, Genetic; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005819:Genetic Markers; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D051704:Sp2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D055153:Stem Cell Niche; D018183:Transplantation Chimera / Q000196:embryology / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D005819:Genetic Markers; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D051704:Sp2 Transcription Factor