The role of Tuba1a in adult hippocampal neurogenesis and the formation of the dentate gyrus.
The multitubulin hypothesis holds that each tubulin isotype serves a unique role with respect to microtubule function. Here we investigate the role of the α-tubulin subunit Tuba1a in adult hippocampal neurogenesis and the formation of the dentate gyrus. Employing birth date labelling and immunohistological markers, we show that mice harbouring an S140G mutation in Tuba1a present with normal neurogenic potential, but that this neurogenesis is often ectopic. Morphological analysis of the dentate gyrus in adulthood revealed a disorganised subgranular zone and a dispersed granule cell layer. We have shown that these anatomical abnormalities are due to defective migration of prospero-homeobox-1-positive neurons and T-box-brain-2-positive progenitors during development. Such migratory defects may also be responsible for the cytoarchitectural defects observed in the dentate gyrus of patients with mutations in TUBA1A.
Institute of Molecular Pathology, Vienna, Austria. keays@imp.ac.at
David A
DA
Keays
James
J
Cleak
Guo-Jen
GJ
Huang
Andrew
A
Edwards
Andreas
A
Braun
Christoph D
CD
Treiber
Ruth
R
Pidsley
Jonathan
J
Flint
D000818:Animals; D018891:Dentate Gyrus / Q000254:growth & development* / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism*
C533522:TUBA1A protein, human; D014404:Tubulin