A caudal-type homeobox gene activity associated with the development and regeneration of the liver

Indirect evidence suggests that a chicken homologue to caudal, CHox-cad, might be involved in the development of endoderm-derived tissues and in the regeneration of the adult intestinal epithelium. Using the adult liver as an experimental system, we have investigated whether CHox-cad expression can be induced by a regenerative stimulus following partial hepatectomy. Under conditions of normal growth, CHox-cad is expressed in the embryonic but not in the adult liver. In the regenerating adult liver, immunohistochemical analyses and in situ hybridization experiments revealed a varying CHox-cad expression pattern extending from 6 h to 11 days posthepatectomy. Early in regeneration, 6 h and 18 h after partial hepatectomy, CHox-cad expression is confined to hepatocytes present in the periphery of the lobuli and to putative hepatic progenitor cells in the portal spaces. At later stages, from 30 h posthepatectomy onwards, CHox-cad activity is detected predominantly in cells of the hepatic progenitor cell compartment, the portal spaces. By day 8, CHox-cad-expressing cells have occupied marginal positions in some portal spaces and appear to penetrate into the periportal parenchyma. With progressing regeneration CHox-cad activity gradually declines reaching low levels in cells of a few portal spaces by day 11 post hepatectomy. As expected for a putative transcription factor, CHox-cad protein is localized to the cell nucleus. Immunodetection of PCNA, a marker of cell proliferation, revealed a much more widespread distribution of mitotic cells as compared to CHox-cad-expressing cells. In the region of overlapping expression domains, coexpression of CHox-cad and PCNA in the same cells was rare in most instances. There is evidence to suggest that CHox-cad is involved in the differentiation of liver progenitor cells to mature hepatocytes. The similarity of the CHox-cad expression pattern in the early developing liver and in the adult regenerating liver may indicate the reactivation of a genetic program operative during early stages of liver morphogenesis.