First Author | Ramos SI | Year | 2020 |
Journal | Dev Cell | Volume | 52 |
Issue | 4 | Pages | 477-491.e8 |
PubMed ID | 32097653 | Mgi Jnum | J:295179 |
Mgi Id | MGI:6458183 | Doi | 10.1016/j.devcel.2020.01.036 |
Citation | Ramos SI, et al. (2020) Tuba8 Drives Differentiation of Cortical Radial Glia into Apical Intermediate Progenitors by Tuning Modifications of Tubulin C Termini. Dev Cell 52(4):477-491.e8 |
abstractText | 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 Delta2 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." |