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The Journal of Neuroscience, August 5, 2009, 29(31):9875-9887; doi:10.1523/JNEUROSCI.2260-09.2009

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Development/Plasticity/Repair
Krüppel-Like Factor 9 Is Necessary for Late-Phase Neuronal Maturation in the Developing Dentate Gyrus and during Adult Hippocampal Neurogenesis

Kimberly N. Scobie,^1,3 Benjamin J. Hall,⁵ Scott A. Wilke,⁶ Kristen C. Klemenhagen,^1,3 Yoshiaki Fujii-Kuriyama,⁷ Anirvan Ghosh,⁶ René Hen,^1,2,3,4 and Amar Sahay^1,3,4

Departments of ¹Neuroscience and Psychiatry and ²Pharmacology, Columbia University, ³Division of Integrative Neuroscience, ⁴New York State Psychiatric Institute, New York, New York 10032, ⁵Department of Cell and Molecular Biology and the Neuroscience Program, Tulane University, New Orleans, Louisiana 70118, ⁶Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093, and ⁷Tsukuba Advanced Alliance Research Center, University of Tsukuba, Tsukuba 305-8577, Japan

Correspondence should be addressed to Dr. René Hen at the above address. Email: rh95{at}columbia.edu

The dentate gyrus (DG) is modified throughout life by integration of new adult-born neurons. Similarities in neuronal maturation during DG development and adult hippocampal neurogenesis suggest that genetically encoded intrinsic regulatory mechanisms underlying these temporally distinct processes are conserved and reused. Here, we identify a novel transcriptional regulator of dentate granule neuron maturation, Krüppel-like factor 9 (Klf-9). We show that Klf-9 expression is induced by neuronal activity and as dentate granule neurons functionally integrate in the developing and adult DG. During development, dentate granule neurons lacking Klf-9 show delayed maturation as reflected by altered expression of early-phase markers, dendritic spine formation, and electrophysiological properties. Adult Klf-9-null mice exhibit normal stem cell proliferation and cell fate specification in the DG but show impaired differentiation of adult-born neurons and decreased neurogenesis-dependent synaptic plasticity. Behavioral analysis of Klf-9-null mice revealed a subtle increase in anxiety-like behavior and an impairment in contextual fear discrimination learning. Thus, Klf-9 is necessary for late-phase maturation of dentate granule neurons both in DG development and during adult hippocampal neurogenesis. Klf-9-dependent neuronal maturation may therefore represent a candidate regulatory mechanism underlying these temporally distinct processes.

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Received May 8, 2009; revised June 18, 2009; accepted June 22, 2009.

Correspondence should be addressed to Dr. René Hen at the above address. Email: rh95{at}columbia.edu

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