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Neuroscience - Physics - Physiology

Restricted Morphological and Behavioral Abnormalities following Ablation of ß-Actin in the Brain
Published: Monday, March 05, 2012
Author: Thomas R. Cheever et al.

by Thomas R. Cheever, Bin Li, James M. Ervasti

The local translation of ß-actin is one mechanism proposed to regulate spatially-restricted actin polymerization crucial for nearly all aspects of neuronal development and function. However, the physiological significance of localized ß-actin translation in neurons has not yet been demonstrated in vivo. To investigate the role of ß-actin in the mammalian central nervous system (CNS), we characterized brain structure and function in a CNS-specific ß-actin knock-out mouse (CNS-ActbKO). ß-actin was rapidly ablated in the embryonic mouse brain, but total actin levels were maintained through upregulation of other actin isoforms during development. CNS-ActbKO mice exhibited partial perinatal lethality while survivors presented with surprisingly restricted histological abnormalities localized to the hippocampus and cerebellum. These tissue morphology defects correlated with profound hyperactivity as well as cognitive and maternal behavior impairments. Finally, we also identified localized defects in axonal crossing of the corpus callosum in CNS-ActbKO mice. These restricted defects occurred despite the fact that primary neurons lacking ß-actin in culture were morphologically normal. Altogether, we identified novel roles for ß-actin in promoting complex CNS tissue architecture while also demonstrating that distinct functions for the ubiquitously expressed ß-actin are surprisingly restricted in vivo.