Abstract
Most adult neurons and glia originate from radial glial progenitors (RGs), a type of stem cell typically extending from the apical to the basal side of the 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 Δ2 cleavage, two post-translational modifications (PTMs) 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.” Radial glial progenitors of the developing mouse cortex differentiate into a more restricted progenitor type, apical intermediate progenitors. Ramos et al. find that Tuba8 drives this differentiation by tuning tyrosination and Δ2 cleavage, post-translational modifications of tubulin C termini, highlighting the functional significance of the “tubulin code” in cortical progenitor differentiation.
Original language | English (US) |
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Pages (from-to) | 477-491.e8 |
Journal | Developmental Cell |
Volume | 52 |
Issue number | 4 |
DOIs | |
State | Published - Feb 24 2020 |
Bibliographical note
Publisher Copyright:© 2020 Elsevier Inc.
Keywords
- apical intermediate progenitor
- cell fate
- cortical progenitor
- radial glia
- tubulin post-translational modification
- tyrosination
- Δ2-tubulin
- Mice, Inbred C57BL
- Cells, Cultured
- Cerebral Cortex/cytology
- Male
- Neurons/cytology
- Neurogenesis
- Mice, Knockout
- Cell Lineage
- Tyrosine/metabolism
- Animals
- Fibroblast Growth Factor 10/physiology
- Female
- Neuroglia/cytology
- Cell Differentiation
- Mice
- Tubulin/physiology
- Neural Stem Cells/cytology
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Journal Article
- Research Support, N.I.H., Extramural