Prenatal deletion of the RNA-binding protein HuD disrupts postnatal cortical circuit maturation and behavior

Erik M. DeBoer, Ricardo Azevedo, Taylor A. Vega, Jesse Brodkin, Wado Akamatsu, Hideyuki Okano, George C. Wagner, Mladen Roko Rasin

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

The proper functions of cortical circuits are dependent upon both appropriate neuronal subtype specification and their maturation to receive appropriate signaling. These events establish a balanced circuit that is important for learning, memory, emotion, and complex motor behaviors. Recent research points to mRN Ametabolism as a key regulator of this development and maturation process.Huantigen D (HuD), an RNA-binding protein, has been implicated in the establishment of neuronal identity and neurite outgrowth in vitro. Therefore, we investigated the role of HuD loss of function on neuron specification and dendritogenesis in vivo using a mouse model.We found that loss of HuD early in development results in a defective early dendritic overgrowth phase and pervasive deficits in neuron specification in the lower neocortical layers and defects in dendritogenesis in the CA3 region of the hippocampus. Subsequent behavioral analysis revealed a deficit in performance of a hippocampus-dependent task: the Morris water maze. Further, HuD knock-out (KO) mice exhibited lower levels of anxiety than their wild-type counterparts and were overall less active. Last, we found that HuD KO mice are more susceptible to auditory-induced seizures, often resulting in death. Our findings suggest that HuD is necessary for the establishment of neocortical and hippocampal circuitry and is critical for their function.

Original languageEnglish
Pages (from-to)3674-3686
Number of pages13
JournalJournal of Neuroscience
Volume34
Issue number10
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Neuroscience(all)

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