Natural variation and genetic covariance in adult hippocampal neurogenesis

Gerd Kempermann, Elissa J. Chesler, Lu Lu, Robert Williams, Fred H. Gage

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Adult hippocampal neurogenesis is highly variable and heritable among laboratory strains of mice. Adult neurogenesis is also remarkably plastic and can be modulated by environment and activity. Here, we provide a systematic quantitative analysis of adult hippocampal neurogenesis in two large genetic reference panels of recombinant inbred strains (BXD and AXB/BXA, n = 52 strains). We combined data on variation in neurogenesis with a new transcriptome database to extract a set of 190 genes with expression patterns that are also highly variable and that covary with rates of (i) cell proliferation, (ii) cell survival, or the numbers of surviving (iii) new neurons, and (iv) astrocytes. Expression of a subset of these neurogenesis-associated transcripts was controlled in cis across the BXD set. These self-modulating genes are particularly interesting candidates to control neurogenesis. Among these were musashi (Msi1h) and prominin1/CD133 (Prom1), both of which are linked to stem-cell maintenance and division. Twelve neurogenesis-associated transcripts had significant cis-acting quantitative trait loci, and, of these, six had plausible biological association with adult neurogenesis (Prom1, Ssbp2, Kcnq2, Ndufs2, Camk4, and Kcnj9). Only one cis-acting candidate was linked to both neurogenesis and gliogenesis, Rapgef6, a downstream target of ras signaling. The use of genetic reference panels coupled with phenotyping and global transcriptome profiling thus allowed insight into the complexity of the genetic control of adult neurogenesis.

Original languageEnglish (US)
Pages (from-to)780-785
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number3
DOIs
StatePublished - Jan 17 2006

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Neurogenesis
Quantitative Trait Loci
Gene Expression Profiling
Transcriptome
Astrocytes
Cell Division
Plastics
Cell Survival
Stem Cells
Maintenance
Cell Proliferation
Databases
Gene Expression
Neurons

All Science Journal Classification (ASJC) codes

  • General

Cite this

Natural variation and genetic covariance in adult hippocampal neurogenesis. / Kempermann, Gerd; Chesler, Elissa J.; Lu, Lu; Williams, Robert; Gage, Fred H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 3, 17.01.2006, p. 780-785.

Research output: Contribution to journalArticle

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