Tuba8 Drives Differentiation of Cortical Radial Glia into Apical Intermediate Progenitors by Tuning Modifications of Tubulin C Termini
Tuba8 Drives Differentiation of Cortical Radial Glia into Apical Intermediate Progenitors by Tuning Modifications of Tubulin C Termini
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Tuba8 通过调节微管蛋白 C 末端的修饰来驱动皮质放射状胶质细胞分化为顶端中间祖细胞
DOI：
10.1016/j.devcel.2020.01.036
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发表时间：
2020
影响因子：
11.8
通讯作者：
Ramos S
中科院分区：
文献类型：
--
作者：
Ramos S
大多数成年神经元和神经胶质细胞起源于放射状神经胶质祖细胞（RGs），这是一种通常从发育中的皮质的顶端延伸到基底侧的干细胞。RG自我更新和分化之间的选择的精确调节对于正常发育至关重要，但这种转变的机制仍然难以捉摸。我们发现，非典型的微管蛋白Tuba 8，瞬时表达在皮质祖细胞，驱动分化的RG顶端中间祖细胞，一个更受限制的祖细胞类型缺乏附着的基底层。这种效应取决于Tuba 8的独特C-末端序列，其拮抗微管蛋白酪氨酸化和Δ2切割，这两种翻译后修饰（PTM）对于RG纤维维持以及直接和间接神经发生之间的转换和最终不同的神经元谱系结果至关重要。我们的工作揭示了发育调节的微管蛋白同种型在祖细胞分化中的指导作用，并为细胞微管蛋白PTM密码子的生物学功能提供了新的见解。"
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."