A fundamental question in biology is how single cells can reliably produce progeny of different cell types. Notch signalling frequently facilitates fate determination. Asymmetric cell division (ACD) often controls segregation of Notch signalling by imposing unequal inheritance of regulators of Notch. Here, we assessed the functional relationship between Notch and ACD in mouse T cell development. To attain immunological specificity, developing T cells must pass through a pivotal stage termed β-selection, which involves Notch signalling and ACD. We assessed functional interactions between Notch1 and ACD during β-selection through direct presentation of Notch ligands, DL1 and DL4, and pharmacological inhibition of Notch signalling. Contrary to prevailing models, we demonstrate that Notch signalling controls the distribution of Notch1 itself and cell fate determinants, α-adaptin and Numb. Furthermore, Notch and CXCR4 signalling cooperated to drive polarity during division. Thus, Notch signalling directly orchestrates ACD, and Notch1 is differentially inherited by sibling cells.This article has an associated First Person interview with the first author of the paper.

中文翻译：

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Notch在控制发育中的T细胞的极性和不对称细胞分裂中的新作用。

生物学中的一个基本问题是单个细胞如何可靠地产生不同细胞类型的后代。陷波信号通常有助于确定命运。不对称细胞分裂（ACD）通常通过施加Notch调节子的不等遗传来控制Notch信号的分离。在这里，我们评估了Notch和ACD在小鼠T细胞发育中的功能关系。为了获得免疫学特异性，发育中的T细胞必须经过称为β选择的关键阶段，该阶段涉及Notch信号传导和ACD。我们通过直接呈现Notch配体，DL1和DL4以及Notch信号传导的药理抑制作用，评估了β选择过程中Notch1和ACD之间的功能相互作用。与现行模型相反，我们证明，Notch信号控制Notch1本身的分布以及细胞命运决定因子α-adaptin和Numb。此外，Notch和CXCR4信令协作以在分割期间驱动极性。因此，Notch信号直接协调ACD，而Notch1被同胞差异遗传。本文与第一作者进行了第一人称访谈。