Kim Dong Hee, Kim Han Rae, Choi Eun Jung, Kim Dong Yeol, Kim Kwang Kon, Kim Byung Sam, Park Jeong Woo, Lee Byung Ju
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.
PLoS One. 2014 Jan 21;9(1):e85898. doi: 10.1371/journal.pone.0085898. eCollection 2014.
NELL2 was first identified as a mammalian homolog of chick NEL (Neural EGF-like) protein. It is almost exclusively expressed in neurons of the rat brain and has been suggested to play a role in neural differentiation. However, there is still no clear evidence for the detailed function of NELL2 in the differentiation of neurons. In this study, we identified NELL2 function during neural differentiation of mouse embryonic carcinoma P19 cells. Endogenous expression of NELL2 in the P19 cells increased in parallel with the neuronal differentiation induced by retinoic acid (RA). We found that the mouse NELL2 promoter contains RA response elements (RAREs) and that treatment with RA increased NELL2 promoter activity. Transfection of P19 cells with NELL2 expression vectors induced a dramatic increase in cell aggregation, resulting in the facilitation of neural differentiation. Moreover, NELL2 significantly increased N-cadherin expression in the P19 cell. These data suggest that NELL2 plays an important role in the regulation of neuronal differentiation via control of N-cadherin expression and cell aggregation.
NELL2最初被鉴定为鸡NEL（神经表皮生长因子样）蛋白的哺乳动物同源物。它几乎只在大鼠大脑的神经元中表达，并被认为在神经分化中发挥作用。然而，关于NELL2在神经元分化中的详细功能仍没有明确的证据。在本研究中，我们确定了NELL2在小鼠胚胎癌P19细胞神经分化过程中的功能。P19细胞中NELL2的内源性表达与视黄酸（RA）诱导的神经元分化平行增加。我们发现小鼠NELL2启动子含有RA反应元件（RAREs），并且用RA处理可增加NELL2启动子活性。用NELL2表达载体转染P19细胞会导致细胞聚集显著增加，从而促进神经分化。此外，NELL2显著增加了P19细胞中N-钙黏蛋白的表达。这些数据表明，NELL2通过控制N-钙黏蛋白的表达和细胞聚集在神经元分化的调节中发挥重要作用。
