PILOT STUDY--MICROTUBULE FUNCTION AFTER PARTIAL HEPATECTOMY

Partial hepatectomy in the rat dramatically disrupts hepatocellular microtubule in the remnant liver, as seen by confocal microscopy of liver sections. The resulting "microtubuleless" hepatocyte has provided us with a unique in vivo system, in which a variety of studies can be carried out. We will examine the mechanism of microtubule disruption, including the role of cell cycle-specific gene products and the effects of hormones and growth factors. We will also determine the effect of microtubule disruption on 1) intracellular transport and sorting of vesicles, a process normally dependent on intact microtubule, and 2) gene targeting, which is greatly facilitated by partial hepatectomy and possibly by the concurrent loss of tubules. These studies, which employ the unique "optical sectioning" capability of the laser scanning confocal microscope, have the advantage of utilizing native hepatocellular tissue rather than cells in culture, permitting us to observe events in a truly physiologic setting.