Identification of a Chr 11 quantitative trait locus that modulates proliferation in the rostral migratory stream of the adult mouse brain

Anna Poon, Zhiyou Li, Gregory W. Wolfe, Lu Lu, Robert Williams, Nancy L. Hayes, Richard S. Nowakowski, Daniel Goldowitz

Research output: Contribution to journalArticle

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Abstract

Neuron production takes place continuously in the rostral migratory stream (RMS) of the adult mammalian brain. The molecular mechanisms that regulate progenitor cell division and differentiation in the RMS remain largely unknown. Here, we surveyed the mouse genome in an unbiased manner to identify candidate gene loci that regulate proliferation in the adult RMS. We quantified neurogenesis in adult C57BL/6J and A/J mice, and 27 recombinant inbred lines derived from those parental strains. We showed that the A/J RMS had greater numbers of bromodeoxyuridine-labeled cells than that of C57BL/6J mice with similar cell cycle parameters, indicating that the differences in the number of bromodeoxyuridine-positive cells reflected the number of proliferating cells between the strains. AXB and BXA recombinant inbred strains demonstrated even greater variation in the numbers of proliferating cells. Genome-wide mapping of this trait revealed that chromosome 11 harbors a significant quantitative trait locus at 116.75 ± 0.75 Mb that affects cell proliferation in the adult RMS. The genomic regions that influence RMS proliferation did not overlap with genomic regions regulating proliferation in the adult subgranular zone of the hippocampal dentate gyrus. On the contrary, a different, suggestive locus that modulates cell proliferation in the subgranular zone was mapped to chromosome 3 at 102 ± 7 Mb. A subset of genes in the chromosome 11 quantitative trait locus region is associated with neurogenesis and cell proliferation. Our findings provide new insights into the genetic control of neural proliferation and an excellent starting point to identify genes critical to this process.

Original languageEnglish (US)
Pages (from-to)523-537
Number of pages15
JournalEuropean Journal of Neuroscience
Volume32
Issue number4
DOIs
StatePublished - Aug 1 2010

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Quantitative Trait Loci
Chromosomes, Human, Pair 11
Neurogenesis
Cell Proliferation
Bromodeoxyuridine
Brain
Cell Count
Genes
Parahippocampal Gyrus
Chromosomes, Human, Pair 3
Chromosome Mapping
Dentate Gyrus
Inbred C57BL Mouse
Cell Division
Cell Differentiation
Cell Cycle
Stem Cells
Genome
Neurons

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Identification of a Chr 11 quantitative trait locus that modulates proliferation in the rostral migratory stream of the adult mouse brain. / Poon, Anna; Li, Zhiyou; Wolfe, Gregory W.; Lu, Lu; Williams, Robert; Hayes, Nancy L.; Nowakowski, Richard S.; Goldowitz, Daniel.

In: European Journal of Neuroscience, Vol. 32, No. 4, 01.08.2010, p. 523-537.

Research output: Contribution to journalArticle

Poon, Anna ; Li, Zhiyou ; Wolfe, Gregory W. ; Lu, Lu ; Williams, Robert ; Hayes, Nancy L. ; Nowakowski, Richard S. ; Goldowitz, Daniel. / Identification of a Chr 11 quantitative trait locus that modulates proliferation in the rostral migratory stream of the adult mouse brain. In: European Journal of Neuroscience. 2010 ; Vol. 32, No. 4. pp. 523-537.
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