Aneuploid mosaicism in the developing and adult cerebellar cortex.
Neuroprogenitor cells (NPCs) in several telencephalic proliferative regions of the mammalian brain, including the embryonic cerebral cortex and postnatal subventricular zone (SVZ), display cell division "defects" in normal cells that result in aneuploid adult progeny. Here, we identify the developing cerebellum as a major, nontelencephalic proliferative region of the vertebrate central nervous system (CNS) that also produces aneuploid NPCs and nonmitotic cells. Mitotic NPCs assessed by metaphase chromosome analyses revealed that 15.3% and 20.8% of cerebellar NPCs are aneuploid at P0 and P7, respectively. By using immunofluorescent analysis of cerebellar NPCs, we show that chromosome segregation defects contribute to the generation of cells with an aneuploid genomic complement. Nonmitotic cells were assessed by fluorescence-activated cell sorting (FACS) coupled with fluorescence in situ hybridization (FISH), which revealed neuronal and nonneuronal aneuploid populations in both the adult mouse and human cerebellum. Taken together, these results demonstrate that the prevalence of neural aneuploidy includes nontelencephalic portions of the neuraxis and suggest that the generation and maintenance of aneuploid cells is a widespread, if not universal, property of central nervous system development and organization.
Westra
Jurjen W
JW
Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, California 92037, USA.
Peterson
Suzanne E
SE
Yung
Yun C
YC
Mutoh
Tetsuji
T
Barral
Serena
S
Chun
Jerold
J
D000375:Aging / Q000235:genetics; D000782:Aneuploidy; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development*; D020090:Chromosome Segregation / Q000235:genetics; D002875:Chromosomes / Q000235:genetics; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008677:Metaphase / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis / Q000235:genetics; D009030:Mosaicism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*