Restricted Morphological and Behavioral Abnormalities following Ablation of β-Actin in the Brain
Abstract
The local translation of β-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 β-actin translation in neurons has not yet been demonstrated in vivo. To investigate the role of β-actin in the mammalian central nervous system (CNS), we characterized brain structure and function in a CNS-specific β-actin knock-out mouse (CNS-ActbKO). β-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 β-actin in culture were morphologically normal. Altogether, we identified novel roles for β-actin in promoting complex CNS tissue architecture while also demonstrating that distinct functions for the ubiquitously expressed β-actin are surprisingly restricted in vivo.Citation
PLoS One. 2012 Mar 5; 7(3):e32970ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0032970
Scopus Count
Related articles
- β-Actin specifically controls cell growth, migration, and the G-actin pool.
- Authors: Bunnell TM, Burbach BJ, Shimizu Y, Ervasti JM
- Issue date: 2011 Nov
- β-actin regulates a heterochromatin landscape essential for optimal induction of neuronal programs during direct reprograming.
- Authors: Xie X, Jankauskas R, Mazari AMA, Drou N, Percipalle P
- Issue date: 2018 Dec
- Characterization of the WAVE1 knock-out mouse: implications for CNS development.
- Authors: Dahl JP, Wang-Dunlop J, Gonzales C, Goad ME, Mark RJ, Kwak SP
- Issue date: 2003 Apr 15
- Delayed embryonic development and impaired cell growth and survival in Actg1 null mice.
- Authors: Bunnell TM, Ervasti JM
- Issue date: 2010 Sep
- Cells lacking β-actin are genetically reprogrammed and maintain conditional migratory capacity.
- Authors: Tondeleir D, Lambrechts A, Müller M, Jonckheere V, Doll T, Vandamme D, Bakkali K, Waterschoot D, Lemaistre M, Debeir O, Decaestecker C, Hinz B, Staes A, Timmerman E, Colaert N, Gevaert K, Vandekerckhove J, Ampe C
- Issue date: 2012 Aug