Natural variation and genetic covariance in adult hippocampal neurogenesis. Export

@article{citeulike:592742, 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.}, address = {Max Delbr\"{o}ck Center for Molecular Medicine, Berlin-Buch, 13125 Berlin, Germany. gerd.kempermann@mdc-berlin.de}, author = {Kempermann, G. and Chesler, E. J. and Lu, L. and Williams, R. W. and Gage, F. H.}, citeulike-article-id = {592742}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0510291103}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16407118}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16407118}, day = {17}, doi = {10.1073/pnas.0510291103}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {adult, cd133, dg, genetics, mouse, musashi1, ng, strains}, month = {January}, number = {3}, pages = {780--785}, posted-at = {2006-04-20 19:23:22}, priority = {2}, title = {Natural variation and genetic covariance in adult hippocampal neurogenesis.}, url = {http://dx.doi.org/10.1073/pnas.0510291103}, volume = {103}, year = {2006} }

TY - JOUR ID - citeulike:592742 L3 - citeulike-article-id:592742 N2 - 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. IS - 3 JF - Proc Natl Acad Sci U S A SN - 0027-8424 AD - Max Delbröck Center for Molecular Medicine, Berlin-Buch, 13125 Berlin, Germany. gerd.kempermann@mdc-berlin.de EP - 785 TI - Natural variation and genetic covariance in adult hippocampal neurogenesis. VL - 103 SP - 780 KW - adult KW - cd133 KW - dg KW - genetics KW - mouse KW - musashi1 KW - ng KW - strains AU - Kempermann, G AU - Chesler, EJ AU - Lu, L AU - Williams, RW AU - Gage, FH PY - 2006/01/17/ UR - http://dx.doi.org/10.1073/pnas.0510291103 ER -