CCN3 overexpression inhibits growth of callosal projections via upregulation of RAB25 = CCN3는 RAB25의 upregulation을 통해 inhibits growth of callosal projections

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Title
CCN3 overexpression inhibits growth of callosal projections via upregulation of RAB25 = CCN3는 RAB25의 upregulation을 통해 inhibits growth of callosal projections
Author(s)
M Park; I J Baek; H Kim; D K Woo; Young-Jun Park; S Shim
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 461, no. 3, pp. 456-462
Publication Year
2015
Abstract
The cysteine-rich 61/connective tissue growth factor 3 (CCN3) is a member of the CCN family of secreted multifunctional proteins involved in a variety of cellular processes including migration, adhesion, and differentiation. Previous studies have shown that CCN3 is expressed in the developing rat central nervous system, and enhanced CCN3 expression is highly correlated with tumorigenesis. However, the expression pattern and influence of abnormal CCN3 expression during mouse cortical development remains to be elucidated. Here, we show that CCN3 expression in mice is first detectable at embryonic day 15 and increases until postnatal day 21. We overexpressed CCN3 in mouse cortical neurons using uni- and bilateral electroporation. Our in vivo overexpression experiments showed that elevated CCN3 expression inhibited the axonal outgrowth of callosal projection neurons. Moreover, we identified the small GTPase RAB25 as a downstream effector molecule of CCN3 using transcriptomic analysis with CCN3 overexpressed in cortical tissue. In vivo ectopic expression of RAB25 or the dominant-negative RAB25-T26N also revealed that the GTPase activity of RAB25 is involved in the CCN3-mediated regulation of neuronal outgrowth. Taken together, our results suggest that tight regulation of CCN3 expression is necessary for normal cortical neuronal connectivity during development, and RAB25 negatively regulates neuronal differentiation as a downstream effector of CCN3.
Keyword
Callosal projectionCCN3CortexNeurite outgrowthRAB25
ISSN
0006-291X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbrc.2015.04.016
Type
Article
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
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