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

2 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

Funding Information:
We thank Drs. B. Berninger, J. Clarke, C. Houart, and O. Marín for their valuable comments on the manuscript; Dr. S. Kato for Fgf10 floxed mice; Drs. N. Heintz and T. Haydar for plasmids; and Ms. A. Arcourt for technical assistance. We are grateful to Dr. L. Cancedda for advice on triple electrode setup and Drs. V. Borrell and L. Lim for valuable advice on revision experiments. This work was supported by the Biotechnology and Biological Sciences Research Council (grants BB/L00562X/1 to S.S. and BB/M007103/1 and BB/R001049/1 to E.V.M.), the Brain & Behaviour Research Foundation (Young Investigator Grant 20881 to S.S.), European Commission ( H2020-MSCA-RISE-2016 ; project ID 734791 to E.V.M.), and the National Institute of Arthritis, Musculoskeletal and Skin Diseases of the National Institutes of Health , USA ( R01AR064195 to Y.K.). S.I.R. was supported by a LIDo studentship from the BBSRC .

Funding Information:
We thank Drs. B. Berninger, J. Clarke, C. Houart, and O. Mar?n for their valuable comments on the manuscript; Dr. S. Kato for Fgf10 floxed mice; Drs. N. Heintz and T. Haydar for plasmids; and Ms. A. Arcourt for technical assistance. We are grateful to Dr. L. Cancedda for advice on triple electrode setup and Drs. V. Borrell and L. Lim for valuable advice on revision experiments. This work was supported by the Biotechnology and Biological Sciences Research Council (grants BB/L00562X/1 to S.S. and BB/M007103/1 and BB/R001049/1 to E.V.M.), the Brain & Behaviour Research Foundation (Young Investigator Grant 20881 to S.S.), European Commission (H2020-MSCA-RISE-2016; project ID 734791 to E.V.M.), and the National Institute of Arthritis, Musculoskeletal and Skin Diseases of the National Institutes of Health, USA (R01AR064195 to Y.K.). S.I.R. was supported by a LIDo studentship from the BBSRC. S.I.R. and S.S. designed and performed all of the experiments and acquired and analyzed the data. M.S. helped with the live imaging analysis. S.I.R. E.V.M. and S.S. wrote the manuscript. Y.K. characterized the Fgf10-floxed and null mice, prepared the samples, and organized the Fgf10KO RNA-seq analysis. E.V.M. analyzed the RNA-seq data. T.K. wrote all of the Fiji analysis programs. The authors declare no competing interests.

Publisher Copyright:
© 2020 Elsevier Inc.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • apical intermediate progenitor
  • cell fate
  • cortical progenitor
  • radial glia
  • tubulin post-translational modification
  • tyrosination
  • Δ2-tubulin

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Tuba8 Drives Differentiation of Cortical Radial Glia into Apical Intermediate Progenitors by Tuning Modifications of Tubulin C Termini'. Together they form a unique fingerprint.

Cite this