Seven-up controls switching of transcription factors that specify temporal identities of Drosophila neuroblasts

Seven-up controls switching of transcription factors that specify temporal identities of Drosophila neuroblasts
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DOI:
10.1016/j.devcel.2004.12.014
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发表时间:
2005-02-01
期刊:
影响因子:
11.8
通讯作者:
Hiromi, Y
Hiromi, Y
中科院分区:
生物学1区
文献类型:
--
作者:
Kanai, MI;Okabe, M;Hiromi, Y

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果蝇神经干细胞(NB)在分裂时不断改变特征,在下一次分裂时产生不同类型的后代。转录因子Hunchback(HB)、Kruppel(KR)、Pdm(PDM)等在每个NB中顺序表达,并作为出生顺序身份的决定因素。NB如何将其表达谱从一种转录因子转换到另一种转录因子还知之甚少。我们表明,HB-KR开关是由核受体七(SVP)。SVP表达局限于NB谱系内的时间限制的子部分。SVP功能的丧失导致几个NB谱系内HB阳性细胞数量的增加,而svp的错误表达导致这些早期出生的神经元的丧失。血统分析提供的证据表明,需要svp在适当的时候关闭HB。因此,svp修改了自我更新的干细胞程序,允许细胞命运的时间顺序变化,从而产生神经元的多样性。
Drosophila neuronal stem cell neuroblasts (NB) constantly change character upon division, to produce a different type of progeny at the next division. Transcription factors Hunchback (HB), Kruppel (KR), Pdm (PDM), etc. are expressed sequentially in each NB and act as determinants of birth-order identity. How a NB switches its expression profile from one transcription factor to the next is poorly understood. We show that the HB-to-KR switch is directed by the nuclear receptor Seven-up (SVP). SVP expression is confined to a temporally restricted subsection within the NB's lineage. Loss of SVP function causes an increase in the number of HB-positive cells within several NB lineages, whereas misexpression of svp leads to the loss of these early-born neurons. Lineage analysis provides evidence that svp is required to switch off HB at the proper time. Thus, svp modifies the self-renewal stem cell program to allow chronological change of cell fates, thereby generating neuronal diversity.