Bridging the Gap: The Importance of TUBA1A α-Tubulin in Forming Midline Commissures.

Developing neurons undergo dramatic morphological changes to appropriately migrate and extend axons to make synaptic connections. The microtubule cytoskeleton, made of α/β-tubulin dimers, drives neurite outgrowth, promotes neuronal growth cone responses, and facilitates intracellular transport of critical cargoes during neurodevelopment. constitutes the majority of α-tubulin in the developing brain and mutations to in humans cause severe brain malformations accompanied by varying neurological defects, collectively termed tubulinopathies.

Neuron-specific mitochondrial oxidative stress results in epilepsy, glucose dysregulation and a striking astrocyte response.

Mitochondrial superoxide (O) production is implicated in aging, neurodegenerative disease, and most recently epilepsy. Yet the specific contribution of neuronal O to these phenomena is unclear. Here, we selectively deleted superoxide dismutase-2 (SOD2) in neuronal basic helix-loop-helix transcription factor (NEX)-expressing cells restricting deletion to a subset of excitatory principle neurons primarily in the forebrain (cortex and hippocampus).

Reduced TUBA1A Tubulin Causes Defects in Trafficking and Impaired Adult Motor Behavior.

Newly born neurons express high levels of TUBA1A α-tubulin to assemble microtubules for neurite extension and to provide tracks for intracellular transport. In the adult brain, expression decreases dramatically. A mouse that harbors a loss-of-function mutation in the gene encoding TUBA1A ( ) allows us to ask whether TUBA1A is important for the function of mature neurons.

Tubulin mutations in brain development disorders: Why haploinsufficiency does not explain TUBA1A tubulinopathies.

The neuronal cytoskeleton performs incredible feats during nervous system development. Extension of neuronal processes, migration, and synapse formation rely on the proper regulation of microtubules. Mutations that disrupt the primary α-tubulin expressed during brain development, TUBA1A, are associated with a spectrum of human brain malformations.

The -Tubulin gene in Brain Development: A Key Ingredient in the Neuronal Isotype Blend.

Microtubules are dynamic cytoskeletal polymers that mediate numerous, essential functions such as axon and dendrite growth and neuron migration throughout brain development. In recent years, sequencing has revealed dominant mutations that disrupt the tubulin protein building blocks of microtubules. These tubulin mutations lead to a spectrum of devastating brain malformations, complex neurological and physical phenotypes, and even fatality.

Epilepsy-causing sequence variations in SIK1 disrupt synaptic activity response gene expression and affect neuronal morphology.

SIK1 syndrome is a newly described developmental epilepsy disorder caused by heterozygous mutations in the salt-inducible kinase SIK1. To better understand the pathophysiology of SIK1 syndrome, we studied the effects of SIK1 pathogenic sequence variations in human neurons. Primary human fetal cortical neurons were transfected with a lentiviral vector to overexpress wild-type and mutant SIK1 protein.