Neural epidermal growth factor-like like protein 2 (NELL2) promotes aggregation of embryonic carcinoma P19 cells by inducing N-cadherin expression

Dong Hee Kim; Han Rae Kim; Eun Jung Choi; Dong Yeol Kim; Kwang Kon Kim; Byung Sam Kim; Jeong Woo Park; Byung Ju Lee

doi:10.1371/journal.pone.0085898

Neural epidermal growth factor-like like protein 2 (NELL2) promotes aggregation of embryonic carcinoma P19 cells by inducing N-cadherin expression

PLoS One. 2014 Jan 21;9(1):e85898. doi: 10.1371/journal.pone.0085898. eCollection 2014.

Authors

Dong Hee Kim¹, Han Rae Kim¹, Eun Jung Choi¹, Dong Yeol Kim¹, Kwang Kon Kim¹, Byung Sam Kim¹, Jeong Woo Park¹, Byung Ju Lee¹

Affiliation

¹ Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

5' Flanking Region / genetics
Animals
Cadherins / metabolism*
Cell Aggregation / drug effects
Cell Aggregation / genetics
Cell Differentiation / drug effects
Cell Differentiation / genetics
Cell Line, Tumor
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Embryonal Carcinoma Stem Cells / metabolism*
Embryonal Carcinoma Stem Cells / pathology*
Gene Expression Regulation, Neoplastic / drug effects
MAP Kinase Signaling System / drug effects
MAP Kinase Signaling System / genetics
Mice
Models, Biological
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Promoter Regions, Genetic / genetics
Protein Binding / drug effects
Protein Binding / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism
Rats
Receptors, Retinoic Acid / metabolism
Response Elements / genetics
Tretinoin / pharmacology

Substances

Cadherins
Nell2 protein, mouse
Nerve Tissue Proteins
RNA, Messenger
Receptors, Retinoic Acid
Tretinoin

Grants and funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF: www.nrf.re.kr) funded by the Ministry of Education, Science and Technology (NRF-2009-0073730), and was also supported by the Original Technology Research Program for Brain Science through the NRF funded by the Ministry of Science, ICT & Future Planning (NRF-2011-0019235). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.