Neural epidermal growth factor-like like protein 2 (NELL2) promotes aggregation of embryonic carcinoma P19 cells by inducing N-cadherin expression.
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.
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.
Dong Hee
DH
Kim
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.
Han Rae
HR
Kim
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.
Eun Jung
EJ
Choi
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.
Dong Yeol
DY
Kim
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.
Kwang Kon
KK
Kim
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.
Byung Sam
BS
Kim
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.
Jeong Woo
JW
Park
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.
Byung Ju
BJ
Lee
D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002449:Cell Aggregation / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D054278:Embryonal Carcinoma Stem Cells / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology
D015820:Cadherins; C491253:Nell2 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014212:Tretinoin