Author

Mandeep Sidhu

Date of Award

2010

Degree Type

Thesis

Degree Name

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Daniel Belliveau

Abstract

Gap junction channels permit intercellular communication through the passage of small molecules and metabolites between adjacent cells and are involved in regulating cellular processes such as homeostasis, differentiation, and proliferation. Connexins (Cx) are the constituent proteins of gap junctions and the neuronal connexin, Cx36, is highly expressed in the developing nervous system. In the present study, the effect of Cx36 on differentiation was investigated by manipulating Cx36 expression levels and inducing differentiation of SH-SY5Y cells. Following retinoic acid induced differentiation of SH- SY5Y cells, Cx36 mRNA expression increased, while Cx45 mRNA expression was unaffected. Cx36 overexpression resulted in diminished retinoic acid induced neuritogenesis, accompanied by decreased expression of differentiation markers, Gap43 and NPY, while knockdown of Cx36 had the reverse effect. Accordingly, overexpression of Cx36 resulted in increased proliferation of SH-SY5Y cells while Cx36 knockdown decreased cell proliferation. In conclusion, Cx36 is a transcriptional target of retinoic acid signaling and acts as a negative regulator of differentiation in SH-SY5Y cells.

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