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在果蝇中枢神经系统中,主调控基因在Notch信号下游发挥作用,以确定神经细胞的命运。

Mastermind acts downstream of notch to specify neuronal cell fates in the Drosophila central nervous system.

作者信息

Schuldt A J, Brand A H

机构信息

Wellcome/CRC Institute and Department of Genetics, Cambridge University, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom.

出版信息

Dev Biol. 1999 Jan 15;205(2):287-95. doi: 10.1006/dbio.1998.9014.

DOI:10.1006/dbio.1998.9014
PMID:9917364
Abstract

In the Drosophila central nervous system, cellular diversity is generated through the asymmetric partitioning of cell fate determinants at cell division. Neural precursors (or neuroblasts) divide in a stem cell lineage to generate a series of ganglion mother cells, each of which divides once to produce a pair of postmitotic neurons or glial cells. An exception to this rule is the MP2 neuroblast, which divides only once to generate two neurons. We screened for genes expressed in the MP2 neuroblast and its progeny as a means of identifying the factors that specify cell fate in the MP2 lineage. We identified a P-element insertion line that expresses the reporter gene, tau-beta-galactosidase, in the MP2 precursor and its progeny, the vMP2 and dMP2 neurons. The transposon disrupts the neurogenic gene, mastermind, but does not lead to neural hyperplasia. However, the vMP2 neuron is transformed into its sibling cell, dMP2. By contrast, expression of a dominant activated form of the Notch receptor in the MP2 lineage transforms dMP2 to vMP2. Notch signalling requires Mastermind, suggesting that Mastermind acts downstream of Notch to determine the vMP2 cell fate. We show that Mastermind plays a similar role in the neurons derived from ganglion mother cells 1-1a and 4-2a, where it specifies the pCC and RP2sib fates, respectively. This suggests that Notch signalling through Mastermind plays a wider role in specifying neuronal identity in the Drosophila central nervous system.

摘要

在果蝇中枢神经系统中,细胞多样性是通过细胞命运决定因子在细胞分裂时的不对称分配产生的。神经前体细胞(或神经母细胞)以干细胞谱系的方式进行分裂,产生一系列神经节母细胞,每个神经节母细胞再分裂一次,产生一对有丝分裂后的神经元或神经胶质细胞。这条规则的一个例外是MP2神经母细胞,它只分裂一次就产生两个神经元。我们筛选了在MP2神经母细胞及其后代中表达的基因,以此作为鉴定在MP2谱系中决定细胞命运的因子的一种方法。我们鉴定出一个P因子插入系,它在MP2前体细胞及其后代vMP2和dMP2神经元中表达报告基因tau-β-半乳糖苷酶。转座子破坏了神经发生基因“主谋”,但不会导致神经增生。然而,vMP2神经元转变为其姐妹细胞dMP2。相比之下,在MP2谱系中表达Notch受体的显性激活形式会使dMP2转变为vMP2。Notch信号传导需要“主谋”,这表明“主谋”在Notch下游发挥作用,以决定vMP2细胞命运。我们发现,“主谋”在源自神经节母细胞1-1a和4-2a的神经元中发挥类似作用,在这些细胞中它分别决定了pCC和RP2sib的命运。这表明通过“主谋”的Notch信号传导在果蝇中枢神经系统中确定神经元身份方面发挥着更广泛的作用。

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