title: Cdk4/cyclinD1 overexpression in neural stem cells shortens G1, delays neurogenesis, and promotes the generation and expansion of basal progenitors.
abstract: During mouse embryonic development, neural progenitors lengthen the G1 phase of the cell cycle and this has been suggested to be a cause, rather than a consequence, of neurogenesis. To investigate whether G1 lengthening alone may cause the switch of cortical progenitors from proliferation to neurogenesis, we manipulated the expression of cdk/cyclin complexes and found that cdk4/cyclinD1 overexpression prevents G1 lengthening without affecting cell growth, cleavage plane, or cell cycle synchrony with interkinetic nuclear migration. Specifically, overexpression of cdk4/cyclinD1 inhibited neurogenesis while increasing the generation and expansion of basal (intermediate) progenitors, resulting in a thicker subventricular zone and larger surface area of the postnatal cortex originating from cdk4/cyclinD1-transfected progenitors. Conversely, lengthening of G1 by cdk4/cyclinD1-RNAi displayed the opposite effects. Thus, G1 lengthening is necessary and sufficient to switch neural progenitors to neurogenesis, and overexpression of cdk4/cyclinD1 can be used to increase progenitor expansion and, perhaps, cortical surface area.
authors.affiliation: DFG-Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD), Medical Faculty, Technische Universität Dresden c/o Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Lange
authors.forename: Wieland B
authors.initials: WB
authors.lastname: Huttner
authors.forename: Federico
authors.initials: F
authors.lastname: Calegari
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D049109:Cell Proliferation; D048429:Cell Size; D019938:Cyclin D1 / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D016193:G1 Phase; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D034622:RNA Interference; D016196:S Phase; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology*
chemical_list: D019927:Cyclin E; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4