Tuba8 Drives Differentiation of Cortical Radial Glia into Apical Intermediate Progenitors by Tuning Modifications of Tubulin C Termini

Susana I. Ramos, Eugene V. Makeyev, Marcelo Salierno, Takashi Kodama, Yasuhiko Kawakami, Setsuko Sahara

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 languageEnglish (US)
Pages (from-to)477-491.e8
JournalDevelopmental Cell
Volume52
Issue number4
DOIs
StatePublished - 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

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