Upregulation of myogenin by N-cadherin adhesion in three-dimensional cultures of skeletal myogenic BHK cells

Abstract

Cells of the baby hamster kidney (BHK) line express the skeletal muscle determining transcription factor MyoD but fail to differentiate. Unlike most skeletal myogenic cells, which express multiple members of the cadherin family of cell-cell adhesion proteins, the BHK cells lack a robust cadherin adhesion system. We previously published that forced expression of N- (or E)-cadherin in BHK cells increases the level of endogenous catenins, mediates strong cell-cell adhesion, and enhances differentiation of BHK cells induced to differentiate by placing them in three-dimensional (3-D) culture (Redfield et al. [1997] J. Cell. Biol. 138:1323-1331). This report demonstrates that N-cadherin adhesion upregulates the protein level of nuclear myogenin in cells induced to differentiate by 3-D culture. Myogenin is a transcription factor required for differentiation of skeletal muscle. It was not detected in monolayer culture, whether the cells expressed N-cadherin or not, nor was it upregulated in 3-D cultures of cells lacking N-cadherin. The activity of two myogenin-chloramphenicol acetyltransferase (CAT) reporter constructs containing 3.7 or 1.1 kb upstream regulatory region of the mouse myogenin gene was increased significantly in N-cadherin-expressing cells induced to differentiate by 3-D culture. Our observations indicate that N-cadherin adhesion stimulates skeletal myogenesis by upregulating myogenin.