title: Conserved molecular signatures of neurogenesis in the hippocampal subgranular zone of rodents and primates.
abstract: The neurogenic potential of the subgranular zone (SGZ) of the hippocampal dentate gyrus is likely to be regulated by molecular cues arising from its complex heterogeneous cellular environment. Through transcriptome analysis using laser microdissection coupled with DNA microarrays, in combination with analysis of genome-wide in situ hybridization data, we identified 363 genes selectively enriched in adult mouse SGZ. These genes reflect expression in the different constituent cell types, including progenitor and dividing cells, immature granule cells, astrocytes, oligodendrocytes and GABAergic interneurons. Similar transcriptional profiling in the rhesus monkey dentate gyrus across postnatal development identified a highly overlapping set of SGZ-enriched genes, which can be divided based on temporal profiles to reflect maturation of glia versus granule neurons. Furthermore, we identified a neurogenesis-related gene network with decreasing postnatal expression that is highly correlated with the declining number of proliferating cells in dentate gyrus over postnatal development. Many of the genes in this network showed similar postnatal downregulation in mouse, suggesting a conservation of molecular mechanisms underlying developmental and adult neurogenesis in rodents and primates. Conditional deletion of Sox4 and Sox11, encoding two neurogenesis-related transcription factors central in this network, produces a mouse with no hippocampus, confirming the crucial role for these genes in regulating hippocampal neurogenesis.
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98103, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Miller
authors.forename: Jason
authors.initials: J
authors.lastname: Nathanson
authors.forename: Daniel
authors.initials: D
authors.lastname: Franjic
authors.forename: Sungbo
authors.initials: S
authors.lastname: Shim
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Dalley
authors.forename: Sheila
authors.initials: S
authors.lastname: Shapouri
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Smith
authors.forename: Susan M
authors.initials: SM
authors.lastname: Sunkin
authors.forename: Amy
authors.initials: A
authors.lastname: Bernard
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Bennett
authors.forename: Chang-Kyu
authors.initials: CK
authors.lastname: Lee
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hawrylycz
authors.forename: Allan R
authors.initials: AR
authors.lastname: Jones
authors.forename: David G
authors.initials: DG
authors.lastname: Amaral
authors.forename: Nenad
authors.initials: N
authors.lastname: Šestan
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.forename: Ed S
authors.initials: ES
authors.lastname: Lein
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D016678:Genome / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D008253:Macaca mulatta / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D055495:Neurogenesis / Q000235:genetics*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism; D062211:Spatio-Temporal Analysis; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D055751:SOXC Transcription Factors; C490793:Sox11 protein, mouse; C489990:Sox4 protein, mouse
keywords: Development; Hippocampus; Neurogenesis; Rhesus monkey; Subgranular zone; Transcriptome