Differentiated horizontal Interneurons clonally expand to form metastatic retinoblastoma in mice
Differentiated horizontal Interneurons clonally expand to form metastatic retinoblastoma in mice
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DOI：
10.1016/j.cell.2007.09.036
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发表时间：
2007-10-19
期刊：
影响因子：
64.5
通讯作者：
Dyer, Michael A.
中科院分区：
文献类型：
--
作者：
Ajioka, Itsuki;Martins, Rodrigo A. P.;Dyer, Michael A.
在神经发生过程中，从祖细胞到分化神经元的过程被认为是单向的和不可逆的。Rb家族蛋白(Rb、p107和p130)在视网膜形成过程中调节细胞周期退出和分化。Rb和p130在视网膜内核层(INL)神经元中冗余表达。我们发现，在成年Rb中，p130缺陷的视网膜p107代偿阻止了INL神经元的异位增殖。然而，p107在这一过程中是单倍体不足的。分化的Rb(-/-)、p107(+/-)、p130(-/-)水平中间神经元重新进入细胞周期，克隆性扩张，形成转移性视网膜母细胞瘤。水平细胞不受Rb+/-；p107(-/-)；p130(-/-)或Rb-/-；p107(-/-)；p130(+/-)的影响，提示一个拷贝的Rb或p130就足以阻止水平增殖。我们在此报告分化的神经元可以增殖并形成癌症，同时保持其分化状态，包括神经突起和突触连接。
During neurogenesis, the progression from a progenitor cell to a differentiated neuron is believed to be unidirectional and irreversible. The Rb family of proteins ( Rb, p107, and p130) regulates cell-cycle exit and differentiation during retinogenesis. Rb and p130 are redundantly expressed in the neurons of the inner nuclear layer (INL) of the retina. We have found that in the adult Rb; p130-deficient retinae p107 compensation prevents ectopic proliferation of INL neurons. However, p107 is haploinsufficient in this process. Differentiated Rb (-/-); p107(+/-); p130(-/-) horizontal interneurons re-entered the cell cycle, clonally expanded, and formed metastatic retinoblastoma. Horizontal cells were not affected in Rb+/-; p107(-/-); p130(-/-) or Rb-/-; p107(-/-); p130(+/-), retinae suggesting that one copy of Rb or p130 was sufficient to prevent horizontal proliferation. We hereby report that differentiated neurons can proliferate and form cancer while maintaining their differentiated state including neurites and synaptic connections.