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

By Kimberly N. Scobie, B. Hall, Scott A. Wilke, K. C. Klemenhagen, Y. Fujii‐Kuriyama, Anirvan Ghosh, R. Hen, Amar Sahay. 2009

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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.

Subfields: Developmental Neuroscience, Genetics, Molecular Biology

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Citations in the corpus

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “In contrast, Prox1 (Lavado et al., 2010), NeuroD (Gao et al., 2009; Kuwabara et al., 2009), and Krüppel-like factor 9 (Scobie et al., 2009) are sequentially required for maturation and survival of new neurons in the adult hippocampus.”
New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? (2010, background): “A transcription factor, krupple-like factor 9, seems to be essential for the survival of adult-born DGCs during this tim”
Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. (2012, unknown): “Third, we confirmed by X-ray irradiation that adultborn DGGCs are crucial for efficient acquisition of the contextual discrimination power in normal mice (Scobie et al., 2009; Tronel et al., 2012; Sahay et al., 2011).”
The role of adult hippocampal neurogenesis in brain health and disease (2018, background): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Table 1 Signals regulating adult hippocampal neurogenesis Stages Regulators Secreted factors and downstream effectors (Morphogens, growth fa”
Entorhinal Cortical Ocean Cells Encode Specific Contexts and Drive Context-Specific Fear Memory. (2015, unknown): “Inputs to CA3 from DG include both developmentally derived old DG-GCs and adult-generated young DG-GCs, which have been shown to play a role in contextual fear memory (Kheirbek et al., 2013).”