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Tuba8 Drives Differentiation of Cortical Radial Glia into Apical Intermediate Progenitors by Tuning Modifications of Tubulin C Termini.
Developmental Cell ( IF 10.7 ) Pub Date : 2020-02-24 , DOI: 10.1016/j.devcel.2020.01.036
Susana I Ramos 1 , Eugene V Makeyev 1 , Marcelo Salierno 1 , Takashi Kodama 2 , Yasuhiko Kawakami 3 , Setsuko Sahara 4
Affiliation  

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."

中文翻译:

Tuba8通过调节微管蛋白C端粒的修饰,将皮质Rad神经胶质细胞分化为顶端中间祖细胞。

大多数成年神经元和神经胶质来自放​​射状神经胶质祖细胞(RGs),这是一种干细胞,通常从发育中的皮层的顶侧延伸到基底侧。RG自我更新和分化之间的选择的精确调节对于正常的发展至关重要,但是这种转变的基础机制仍然难以捉摸。我们显示,非典型的微管蛋白Tuba8,在皮质祖细胞中瞬时表达,驱动RGs分化为顶端中间祖细胞,是一种受限制的祖细胞类型,缺乏对基底层的附着。这种作用取决于Tuba8独特的C端序列,该序列可拮抗微管蛋白的酪氨酸化和Δ2裂解,两个翻译后修饰(PTM)对于RG纤维的维持以及直接和间接神经发生以及最终独特的神经元谱系结局之间的转换至关重要。我们的工作揭示了发育受调节的微管蛋白同种型在祖细胞分化中的指导作用,并提供了对细胞微管蛋白PTM“代码”的生物学功能的新见解。
更新日期:2020-02-24
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