Numb antagonizes notch signaling to specify sibling neuron cell fates
Numb antagonizes notch signaling to specify sibling neuron cell fates
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DOI：
10.1016/s0896-6273(00)80277-9
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发表时间：
1996-07-01
期刊：
影响因子：
16.2
通讯作者：
Doe, CQ
中科院分区：
文献类型：
--
作者：
Spana, EP;Doe, CQ
不对称细胞分裂在哺乳动物和果蝇中枢神经系统（CNS）神经元多样性的建立中起关键作用，但所涉及的机制大多未知。果蝇的MP2前体不对称分裂产生dMP2/vMP2中间神经元。Delta - Notch信号是确定vMP2命运所必需的，而定位决定因子Numb被分隔到dMP2中，是确定dMP2命运所必需的。Notch；numb双突变体有两个dMP2神经元；因此，Numb对于dMP2命运不是必需的，但拮抗Delta - Notch的“vMP2”信号。体内Delta表达和体外培养实验表明，vMP2命运是由来自MP2谱系之外的“诱导”信号所确定的。因此，内在和外在的信号汇聚以确定MP2细胞谱系中的两种细胞命运。
Asymmetric cell divisions play a key role in establishing neuronal diversity in the mammalian and Drosophila CNS, but the mechanisms involved are mostly unknown. The Drosophila MP2 precursor divides asymmetrically to generate the dMP2/vMP2 interneurons. Delta-Notch signaling is required to specify vMP2 fate, whereas the localized determinant Numb is segregated into dMP2 and is required to specify dMP2 fate. Notch; numb double mutants have two dMP2 neurons; hence, Numb is not required for dMP2 fate, but antagonizes the Delta-Notch ''vMP2'' signal. In vivo Delta expression and in vitro culture experiments show that vMP2 fate is specified by an ''inductive'' signal from outside the MP2 lineage. Thus, intrinsic and extrinsic cues converge to specify binary cell fates in the MP2 cell lineage.