Wang Jinbo, Chitturi Jyothsna, Ge Qinglan, Laskova Valeriya, Wang Wei, Li Xia, Ding Mei, Zhen Mei, Huang Xun
State Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
Lunenfeld and Tanebaum Research Institute, University of Toronto, Toronto, Ontario, Canada M5G 1X5.
Development. 2015 Apr 15;142(8):1447-57. doi: 10.1242/dev.119479. Epub 2015 Mar 19.
Mechanisms that regulate apoptosis in a temporal and lineage-specific manner remain poorly understood. The COE (Collier/Olf/EBF) transcription factors have been implicated in the development of many cell types, including neurons. Here, we show that the sole Caenorhabditis elegans COE protein, UNC-3, together with a histone acetyltransferase, CBP-1/P300, specifies lineage-specific apoptosis and certain aspects of neurite trajectory. During embryogenesis, the RID progenitor cell gives rise to the RID neuron and RID sister cell; the latter undergoes apoptosis shortly after cell division upon expression of the pro-apoptotic gene egl-1. We observe UNC-3 expression in the RID progenitor, and the absence of UNC-3 results in the failure of the RID lineage to express a Pegl-1::GFP reporter and in the survival of the RID sister cell. Lastly, UNC-3 interacts with CBP-1, and cbp-1 mutants exhibit a similar RID phenotype to unc-3. Thus, in addition to playing a role in neuronal terminal differentiation, UNC-3 is a cell lineage-specific regulator of apoptosis.
以时间和谱系特异性方式调节细胞凋亡的机制仍知之甚少。COE（Collier/Olf/EBF）转录因子与包括神经元在内的多种细胞类型的发育有关。在此，我们表明秀丽隐杆线虫唯一的COE蛋白UNC-3与组蛋白乙酰转移酶CBP-1/P300一起，决定了谱系特异性凋亡和神经突轨迹的某些方面。在胚胎发生过程中，RID祖细胞产生RID神经元和RID姐妹细胞；后者在细胞分裂后不久，在促凋亡基因egl-1表达时发生凋亡。我们观察到UNC-3在RID祖细胞中表达，并且UNC-3的缺失导致RID谱系无法表达Pegl-1::GFP报告基因，以及RID姐妹细胞存活。最后，UNC-3与CBP-1相互作用，并且cbp-1突变体表现出与unc-3相似的RID表型。因此，除了在神经元终末分化中发挥作用外，UNC-3还是细胞谱系特异性的凋亡调节因子。
