Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system
Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system
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DOI：
10.1038/ncomms5484
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发表时间：
2014-07-01
影响因子：
16.6
通讯作者：
Giangrande, Angela
中科院分区：
文献类型：
--
作者：
Flici, Hakima;Cattenoz, Pierre B.;Giangrande, Angela
多能性前体是可塑性细胞，在正确的数量、地点和时间产生不同的、稳定的命运，从而形成组织和器官。虽然已知命运决定因素可以触发特定的转录程序，但驱动多能前体向稳定和特定身份发展的分子途径仍然知之甚少。在这里，我们证明，在果蝇的神经前体中，胶质细胞决定性缺失（Gcm）就像一个“定时炸弹”，一旦胶质细胞程序被稳定激活，它就会触发自身的降解。这需要一系列转录和转录后循环，其中Gcm目标首先影响命运决定因子的表达，然后影响乙酰化，从而控制Gcm水平和稳定性。回路之间有缺陷的内平衡改变了神经元与胶质细胞的比例，并将细胞冻结在中间胶质/神经元表型中。总之，我们确定了一种触发细胞身份的有效策略，这是一种在癌症等病理条件下改变的过程。
Multipotent precursors are plastic cells that generate different, stable fates at the correct number, place and time, to allow tissue and organ formation. While fate determinants are known to trigger specific transcriptional programs, the molecular pathway driving the progression from multipotent precursors towards stable and specific identities remains poorly understood. Here we demonstrate that, in Drosophila neural precursors, the glial determinant glial cell missing (Gcm) acts as a 'time bomb' and triggers its own degradation once the glial programme is stably activated. This requires a sequence of transcriptional and post-transcriptional loops, whereby a Gcm target first affects the expression and then acetylation of the fate determinant, thus controlling Gcm levels and stability over time. Defective homeostasis between the loops alters the neuron: glia ratio and freezes cells in an intermediate glial/neuronal phenotype. In sum, we identify an efficient strategy triggering cell identity, a process altered in pathological conditions such as cancer.