Tuba8 drives differentiation of cortical radial glia into apical intermediate progenitors by tuning modifications of tubulin C-termini

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Abstract

Most adult neurons and glia originate from radial glial progenitors (RGs), a type of stem cells typically extending from the apical to the basal side of developing cortex. Precise regulation of the choice between RG self-renewal and differentiation is critical for normal development, but the mechanisms underlying this transition remain elusive. We show that the non-canonical tubulin Tuba8, transiently expressed in cortical progenitors, drives differentiation of RGs into apical intermediate progenitors, a more restricted progenitor type lacking attachment to the basal lamina. This effect depends on the unique C-terminal sequence of Tuba8 that antagonizes tubulin tyrosination and ∆2-cleavage, two post-translational modifications (PTM) essential for RG fiber maintenance and the switch between direct and indirect neurogenesis and ultimately distinct neuronal lineage outcomes. Our work uncovers an instructive role of a developmentally regulated tubulin isotype in progenitor differentiation and provides new insights into biological functions of the cellular tubulin PTM "code".
Original languageEnglish
JournalDevelopmental Cell
Volume52
Issue number4
Publication statusAccepted/In press - 29 Jan 2020

Keywords

  • Cortical progenitor, radial glia, apical intermediate progenitor, cell fate, tubulin posttranslational modification, tyrosination, ∆2-tubulin

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