TUBB5 and its disease-associated mutations influence the terminal differentiation and dendritic spine densities of cerebral cortical neurons
MetadataShow full item record
© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: email@example.com. The microtubule cytoskeleton is critical for the generation and maturation of neurons in the developing mammalian nervous system. We have previously shown that mutations in the ß-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities in humans. While it is known that TUBB5 is necessary for the proper generation and migration of neurons, little is understood of the role it plays in neuronal differentiation and connectivity. Here, we report that perturbations to TUBB5 disrupt the morphology of cortical neurons, their neuronal complexity, axonal outgrowth, as well as the density and shape of dendritic spines in the postnatal murine cortex. The features we describe are consistent with defects in synaptic signaling. Cellular-based assays have revealed that TUBB5 substitutions have the capacity to alter the dynamic properties and polymerization rates of the microtubule cytoskeleton. Together, our studies show that TUBB5 is essential for neuronal differentiation and dendritic spine formation in vivo, providing insight into the underlying cellular pathology associated with TUBB5 disease states.
Showing items related by title, author, creator and subject.
Liang, Huazheng; Paxinos, George; Watson, Charles (2012)We studied the organization and spinal projection of the mouse red nucleus with a range of techniques (Nissl stain, immunofluorescence, retrograde tracer injections into the spinal cord, anterograde tracer injections into ...
Distribution of neurons across functional areas in the mouse cerebral cortex reveals quantitatively different cortical zonesHerculano-Houzel, S.; Watson, Charles; Paxinos, G. (2013)How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005) to analyze the distribution of neurons across the entire isocortex ...
Fu, Y.; Yu, Y.; Paxinos, G.; Watson, Charles; Rusznák, Z. (2015)Although the impact of aging on the function of the central nervous system is known, only a limited amount of information is available about accompanying changes affecting the cellular composition of the brain and spinal ...