Pearson Bret J, Doe Chris Q
Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, University of Oregon 1254, Eugene, Oregon 97403, USA.
Nature. 2003 Oct 9;425(6958):624-8. doi: 10.1038/nature01910.
Individual neural progenitors generate different cell types in a reproducible order in the retina, cerebral cortex and probably in the spinal cord. It is unknown how neural progenitors change over time to generate different cell types. It has been proposed that progenitors undergo progressive restriction or transit through distinct competence states; however, the underlying molecular mechanisms remain unclear. Here we investigate neural progenitor competence and temporal identity using an in vivo genetic system--Drosophila neuroblasts--where the Hunchback transcription factor is necessary and sufficient to specify early-born cell types. We show that neuroblasts gradually lose competence to generate early-born fates in response to Hunchback, similar to progressive restriction models, and that competence to acquire early-born fates is present in mitotic precursors but is lost in post-mitotic neurons. These results match those observed in vertebrate systems, and establish Drosophila neuroblasts as a model system for the molecular genetic analysis of neural progenitor competence and plasticity.
单个神经祖细胞在视网膜、大脑皮层以及可能在脊髓中以可重复的顺序产生不同的细胞类型。目前尚不清楚神经祖细胞如何随时间变化以产生不同的细胞类型。有人提出,祖细胞会经历渐进性限制或通过不同的能力状态转变;然而,其潜在的分子机制仍不清楚。在这里,我们使用一种体内遗传系统——果蝇神经母细胞——来研究神经祖细胞的能力和时间特性,在该系统中,驼背转录因子对于指定早期产生的细胞类型是必要且充分的。我们表明,神经母细胞会随着对驼背的反应而逐渐失去产生早期命运的能力,这与渐进性限制模型类似,并且获得早期命运的能力存在于有丝分裂前体中,但在有丝分裂后神经元中丧失。这些结果与在脊椎动物系统中观察到的结果相符,并将果蝇神经母细胞确立为用于神经祖细胞能力和可塑性分子遗传分析的模型系统。