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MicroRNA-mediated disruption of dendritogenesis during a critical period of development influences cognitive capacity later in life.

  • Author(s): Lin, Quan
  • Ponnusamy, Ravikumar
  • Widagdo, Jocelyn
  • Choi, Jung A
  • Ge, Weihong
  • Probst, Christine
  • Buckley, Tyler
  • Lou, Mimi
  • Bredy, Timothy W
  • Fanselow, Michael S
  • Ye, Keqiang
  • Sun, Yi E
  • et al.
Abstract

The prenatal period of cortical development is important for the establishment of neural circuitry and functional connectivity of the brain; however, the molecular mechanisms underlying this process remain unclear. Here we report that disruption of the actin-cytoskeletal network in the developing mouse prefrontal cortex alters dendritic morphogenesis and synapse formation, leading to enhanced formation of fear-related memory in adulthood. These effects are mediated by a brain-enriched microRNA, miR-9, through its negative regulation of diaphanous homologous protein 1 (Diap1), a key organizer of the actin cytoskeletal assembly. Our findings not only revealed important regulation of dendritogenesis and synaptogenesis during early brain development but also demonstrated a tight link between these early developmental events and cognitive functions later in life.

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