The majority of adult neurons and glia originate from radial glial progenitors (RGs) but how the balance between RG self-renewal versus cell differentiation is achieved - critical to normal development - is not well understood.
The Sahara lab (Susana Ramos & Setsuko Sahara), along with Eugene Makeyev and Marcelo Salierno, examine the role of non-canonical tubulin, Tuba8, which is transiently expressed in cortical progenitors in their new paper in Developmental Cell. They showed that Tuba8 drives the differentiation of RGs into apical intermediate progenitors – a more restricted progenitor type – lacking attachment to the basal lamina.
This differentiation is dependent on the unique C-terminal sequence of Tuba8 that antagonises tubulin tyrosination and Δ2-cleavage – two post-translational modifications essential for RG fibre maintenance and the switch between direct and indirect neurogenesis, and ultimately, distinct neuronal lineage outcomes.
Developmentally regulated tubulin isotype, Tuba8, has an instructive role in progenitor differentiation, afforded by its resistance to and ability to tune C-terminal tyrosination and Δ2-cleavage. These interesting findings could be important for understanding neurodevelopment and its disorders given that Tuba8 has previously been linked with polymicrogyria.
“Our study provides insight into one of the most important cellular building blocks in brain development. Radial glial progenitor (RGP) cells are responsible for producing most neutrons and glia in the developing brain and, for the first time, we show that a protein called Tuba8 modulated their decision of whether to differentiate or renew.”