title: Prenatal deletion of the RNA-binding protein HuD disrupts postnatal cortical circuit maturation and behavior.
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 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 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.
authors.affiliation: Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School and Department of Psychology, Rutgers University, Piscataway, New Jersey 08854, University of California, Berkeley, California 94704, Behavioral Instruments, Hillsborough, New Jersey 08854, and Department of Physiology, Keio University, Tokyo 160-8582, Japan.
authors.forename: Erik M
authors.initials: EM
authors.lastname: DeBoer
authors.forename: Ricardo
authors.initials: R
authors.lastname: Azevedo
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Vega
authors.forename: Jesse
authors.initials: J
authors.lastname: Brodkin
authors.forename: Wado
authors.initials: W
authors.lastname: Akamatsu
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: George C
authors.initials: GC
authors.lastname: Wagner
authors.forename: Mladen-Roko
authors.initials: MR
authors.lastname: Rasin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051959:ELAV Proteins / Q000172:deficiency* / Q000235:genetics; D000067779:ELAV-Like Protein 4; D005260:Female; D017353:Gene Deletion; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000254:growth & development* / Q000378:metabolism*; D009415:Nerve Net / Q000254:growth & development* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics; D012640:Seizures / Q000235:genetics / Q000378:metabolism
chemical_list: D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498011:Elavl4 protein, mouse; D016601:RNA-Binding Proteins