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

TY - JOUR

T1 - Tuba8 drives differentiation of cortical radial glia into apical intermediate progenitors by tuning modifications of tubulin C-termini

AU - Teixeira E Rodrigues Ramos, Susana Isabel

AU - Makeyev, Eugene

AU - Salierno, Marcelo Javier

AU - Kodama, Takashi

AU - Kawakami, Yasuhiko

AU - Sahara, Setsuko

PY - 2020/1/29

Y1 - 2020/1/29

N2 - 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".

AB - 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".

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

M3 - Article

SN - 1534-5807

VL - 52

JO - Developmental Cell

JF - Developmental Cell

IS - 4

ER -