Expression and potential role of the extracellular matrix in hepatic ontogenesis: a review

Studies from a number of laboratories have provided information on the temporal and spatial expression of a variety of extracellular matrix (ECM) components in the developing liver and insight into their potential roles in hepatogenesis. Collagen type IV and laminin are present in the basement membranes of the capsular mesothelium, vascular structures of the portal and hepatic vein branches, and the ductular elements of the developing liver. The mesothelial, vascular, and ductular epithelial cells synthesize laminin and type IV collagen. In contrast, fibronectin and type I collagen are restricted to the adjacent or surrounding interstitium of those ductal and vascular elements, but are not within the basement membrane proper. The hepatic perisinusoidal space (Space of Disse) of the fetal rat develops a delicate extracellular matrix by 12.5 days of gestation, which is characterized by banded collagen fibrils and bundles associated with filamentous and flocculent material. Fibronectin, laminin, and collagen types I, III, and IV are present in the developing perisinusoidal space by this early gestational date, with laminin being the most prevalent component detected. The laminin chains localized to that region in the fetal/neonatal period are alpha 2, beta 1, beta 2, and gamma 1, whereas the alpha 1 chain of laminin is absent from the developing Space of Disse. Similar data have been reported on the laminin phenotype in the perisinusoidal space during hepatic regeneration. Electron microscopy immunohistochemistry studies have demonstrated that the sinusoidal lining cells and hepatocytes synthesize these ECM proteins during hepatogenesis. By 6 to 8 weeks of postnatal life, laminin is not detectable in the perisinusoidal space. Both the transient expression of laminin and the similarity of the laminin chain phenotype expressed in the perisinusoidal space in the developing and regenerating liver suggests a role for this protein in the organization of the hepatic lobule in those forms of hepatic morphogenesis.