Fibrillin-rich microfibrils - structural and instructive determinants of mammalian development and physiology.

Fibrillin-rich microfibrils have emerged recently as an informative model system in which to study fundamental questions related to extracellular matrix biology and connective tissue pathophysiology. As a result, these studies have yielded novel clinical concepts and promising therapeutic strategies. These achievements have been based on the realization from studies of genetically engineered mice that mutations in fibrillin-rich microfibrils impair both the structural integrity of connective tissues and signaling events by TGF-beta/BMP superfamily members. In this view, fibrillin-rich microfibrils represent architectural assemblies that specify the concentration and timely release of local effectors of morphogenesis and tissue remodeling, in addition to conferring structural integrity to individual organ systems. This review summarizes the evidence supporting our current understanding of the structural and instructive roles that fibrillin-rich microfibrils play during embryonic development and in human diseases.