Alteration of cell adhesion and cell cycle properties of ES cells by an inducible dominant interfering Myb mutant

The Myb transcription factors, c-Myb, A-Myb, and B-Myb, regulate cell diffe rentiation and/or proliferation. To investigate the role of B-Myb in embryo genesis, we introduced an inducible dominant interfering Myb protein (MERT) into embryonic stem (ES) cells, which express B-Myb as an exclusive member of Myb family. Disruption of normal B-Myb function by the conditional acti vation of MERT caused a drastic morphological alteration of ES cells and G( 1)-S cell cycle arrest. The inhibition of B-Myb function by MERT dissociate d tightly packed ES cell colonies into dispersed single cells that subseque ntly detached from the culture dish. Cell adhesion analyses revealed that s uppression of B-Myb function reduced the adhesion with extracellular matrix proteins, such as laminin, collagen, and fibronectin, This reduction was p resumably due to decreased cell surface expression of beta1 integrin, Embry oid body formation was also severely retarded by the activation of MERT, Th is impairment was attributed to reduced expression of E-cadherin, which fun ctions as a homophilic intercellular adhesion molecule. Simultaneously, blo cking B-Myb function did not alter the expression of differentiation marker s. Our data indicate that B-Myb plays important roles in regulating cell ad hesion and cell cycle progression. These results are well consistent with t he recent report on the phenotype of B-Myb null mice and show that the regu lation of cell adhesion is an important B-Myb function that has not yet bee n assumed.