Prenatal Deletion of the RNA-Binding Protein HuD Disrupts Postnatal Cortical Circuit Maturation and Behavior
この論文をさがす
説明
<jats:p>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 mRNA metabolism as a key regulator of this development and maturation process. Hu antigen D (HuD), an RNA-binding protein, has been implicated in the establishment of neuronal identity and neurite outgrowth<jats:italic>in vitro</jats:italic>. Therefore, we investigated the role of HuD loss of function on neuron specification and dendritogenesis<jats:italic>in vivo</jats:italic>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,<jats:italic>HuD</jats:italic>knock-out (KO) mice exhibited lower levels of anxiety than their wild-type counterparts and were overall less active. Last, we found that<jats:italic>HuD</jats:italic>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.</jats:p>
収録刊行物
-
- The Journal of Neuroscience
-
The Journal of Neuroscience 34 (10), 3674-3686, 2014-03-05
Society for Neuroscience