MODULATION OF CONNEXINS DURING DIFFERENTIATION OF OVAL CELLS INTO HEPATOCYTES

The connexins are a family of related gap-junction proteins, implicate d in embryonic development, cell growth control, and cellular differen tiation. To identify connexins involved in liver cell differentiation, both in vivo and in vitro systems were employed to study expression o f connexins 26, 32, and 43. Northern blot analysis and in situ hybridi zation were used to measure the levels of connexin expression and cell ular localization of the transcripts, respectively. Normal liver expre ssed high connexin 32, low connexin 26, and barely detectable connexin 43. In vivo proliferation and differentiation of oval cells was at fi rst accompanied by increased connexin 43 and decreased connexin 32 exp ression; later as the oval cells differentiated into hepatocytes, conn exin 43 disappeared and connexin 32 increased to control levels. In si tu hybridization showed that both oval cells and bile duct epithelial cells, but not hepatocytes, expressed connexin 43. A switch from conne xin 43 to connexin 32 expression was observed following in vitro trans formation and differentiation of rat liver epithelial cells toward the hepatocytic lineage. These results suggest that early progenitor cell s in the liver express connexin 43 and a switch from connexin 43 to co nnexin 32 may signal commitment to hepatocytic differentiation. (C) 19 94 Academic Press, Inc.