MRG15, a component of HAT and HDAC complexes, is essential for proliferation and differentiation of neural precursor cells.
MRG15, a component of HAT and HDAC complexes, is essential for proliferation and differentiation of neural precursor cells.
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DOI：
10.1002/jnr.21976
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发表时间：
2009-05-15
影响因子：
4.2
通讯作者：
Tominaga, Kaoru
中科院分区：
文献类型：
--
作者：
Chen, Meizhen;Takano-Maruyama, Masumi;Pereira-Smith, Olivia M.;Gaufo, Gary O.;Tominaga, Kaoru
发育过程中的神经发生依赖于神经前体细胞的自我更新和分化的协调调节。染色质调节是神经前体细胞自我更新活性和命运决定的关键步骤。然而，这种调控的分子机制(S)还不完全清楚。在这里，我们首次证明了染色质调节因子MRG15对于神经前体细胞的增殖和神经命运的决定是重要的。MRG15缺陷型胚胎脑神经上皮细胞较对照组明显变薄，且该区域的凋亡细胞增多。我们从MRG15缺陷和野生型胚胎全脑中分离出神经前体细胞，并制备神经球，以测定这些细胞的体外自我更新和分化能力。来自mrg15缺陷胚胎的神经球培养比来自野生型的神经球生长效率更低。BrdU掺入法检测神经前体细胞的增殖能力发现，在体外培养过程中，MRG15缺陷的神经前体细胞的增殖能力降低，细胞凋亡率没有增加。MRG15缺陷的神经前体细胞增殖减少很可能是MRG15缺陷的胚胎脑中神经上皮细胞变薄的原因。此外，我们还证明了在体外，MRG15缺陷的神经前体细胞在向神经元分化方面存在缺陷。我们的结果表明，MRG15在神经发生中具有多种功能，并为这种染色质调节因子定义了一个新的角色，它在发育过程中整合了细胞增殖和细胞命运的决定。
Neurogenesis during development depends on the coordinated regulation of self-renewal and differentiation of neural precursor cells. Chromatin regulation is a key step in self-renewal activity and fate decision of neural precursor cells. However, the molecular mechanism(s) of this regulation is not fully understood. Here, we demonstrate for the first time that MRG15, a chromatin regulator, is important for proliferation and neural fate decision of neural precursor cells. Neuroepithelia from Mrg15 deficient embryonic brain are much thinner than those from control, and apoptotic cells increase in this region. We isolated neural precursor cells from Mrg15 deficient and wild-type embryonic whole brains and produced neurospheres to measure the self-renewal and differentiation abilities of these cells in vitro. Neurospheres culture from Mrg15 deficient embryo grew less-efficiently than those from wild-type. Measurement of proliferation, using BrdU incorporation, revealed that Mrg15 deficient neural precursor cells have reduced proliferation ability and apoptotic cells do not increase during in vitro culture. The reduced proliferation of Mrg15 deficient neural precursor cells most likely accounts for the thinner neuroepithelia in Mrg15 deficient embryonic brain. Moreover, we also demonstrate Mrg15 deficient neural precursor cells are defective in differentiation into neurons in vitro. Our results demonstrate that MRG15 has more than one function in neurogenesis and defines a novel role for this chromatin regulator that integrates proliferation and cell-fate determination in neurogenesis during development.
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影响因子：
64.5
作者：
Keogh, MC;Kurdistani, SK;Krogan, NJ
通讯作者：
Krogan, NJ
影响因子：
4.8
作者：
Eisen, A;Utley, RT;Côté, J
通讯作者：
Côté, J
影响因子：
2.7
作者：
Reynolds, BA;Weiss, S
通讯作者：
Weiss, S
影响因子：
2.1
作者：
Hayakawa, Tomohiro;Ohtani, Yasuko;Nakayama, Jun-ichi
通讯作者：
Nakayama, Jun-ichi
DOI：
10.1073/pnas.0407643101
发表时间：
2004-11-23
影响因子：
11.1
作者：
Hsieh, J;Nakashima, K;Gage, FH
通讯作者：
Gage, FH