TUBB5 and its disease-associated mutations influence the terminal differentiation and dendritic spine densities of cerebral cortical neurons
Linh Ngo, Matilda Haas, Zhengdong Qu, Shan Shan Li, Jennifer Zenker, Kathleen Sue Lyn Teng, Jenny Margaret Gunnersen, Martin Breuss, Mark Habgood, David Anthony Keays, Julian Ik-Tsen Heng
HUMAN MOLECULAR GENETICS | OXFORD UNIV PRESS | Published : 2014
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 β-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 consist..View full abstract
Awarded by FWF
Awarded by NH&MRC Career Development Fellowship
Awarded by Austrian Science Fund (FWF)
The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. D.A.K. acknowledges the generous support of Boehringer Ingelheim and the following FWF grants (P24367, P21092 and I914). J.I.H. is supported by an NH&MRC Career Development Fellowship (ID:1011505), as well as a Monash Senior Research Fellowship.