Institute of Neuroscience, Institute of Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403, USA.
Development. 2010 May;137(9):1421-30. doi: 10.1242/dev.048678. Epub 2010 Mar 24.
The Hunchback/Ikaros family of zinc-finger transcription factors is essential for specifying the anterior/posterior body axis in insects, the fate of early-born pioneer neurons in Drosophila, and for retinal and immune development in mammals. Hunchback/Ikaros proteins can directly activate or repress target gene transcription during early insect development, but their mode of action during neural development is unknown. Here, we use recombineering to generate a series of Hunchback domain deletion variants and assay their function during neurogenesis in the absence of endogenous Hunchback. Previous studies have shown that Hunchback can specify early-born neuronal identity and maintain 'young' neural progenitor (neuroblast) competence. We identify two conserved domains required for Hunchback-mediated transcriptional repression, and show that transcriptional repression is necessary and sufficient to induce early-born neuronal identity and maintain neuroblast competence. We identify pdm2 as a direct target gene that must be repressed to maintain competence, but show that additional genes must also be repressed. We propose that Hunchback maintains early neuroblast competence by silencing a suite of late-expressed genes.
锌指转录因子 Hunchback/Ikaros 家族对于昆虫体轴的前/后向特化、果蝇中早出生的先驱神经元的命运以及哺乳动物的视网膜和免疫系统发育是必不可少的。Hunchback/Ikaros 蛋白在昆虫早期发育过程中可以直接激活或抑制靶基因转录,但它们在神经发育过程中的作用方式尚不清楚。在这里,我们使用重组酶生成了一系列 Hunchback 结构域缺失变体,并在没有内源性 Hunchback 的情况下检测了它们在神经发生过程中的功能。先前的研究表明,Hunchback 可以指定早出生的神经元身份并维持“年轻”的神经祖细胞(神经母细胞)的能力。我们确定了两个保守的结构域对于 Hunchback 介导的转录抑制是必需的,并表明转录抑制对于诱导早出生的神经元身份和维持神经母细胞能力是必要和充分的。我们确定了 pdm2 作为维持能力所必需的直接靶基因,但表明还必须抑制其他基因。我们提出 Hunchback 通过沉默一组晚期表达的基因来维持早期神经母细胞的能力。