The
fibrillins, large extracellular matrix molecules, are polymerized to form "microfibrils." The
fibrillin microfibril scaffold is populated by microfibril-associated
proteins and by
growth factors, which are likely to be latent. The scaffold, associated
proteins, and bound
growth factors, together with cellular receptors that can sense the microfibril matrix, constitute the
fibrillin microenvironment. Activation of TGFβ signaling is associated with the
Marfan syndrome, which is caused by mutations in
fibrillin-1. Today we know that mutations in
fibrillin-1 cause the
Marfan syndrome as well as
Weill-Marchesani syndrome (and other acromelic dysplasias) and result in opposite clinical phenotypes: tall or short stature;
arachnodactyly or
brachydactyly;
joint hypermobility or stiff joints; hypomuscularity or hypermuscularity. We also know that these different syndromes are associated with different structural abnormalities in the
fibrillin microfibril scaffold and perhaps with specific cellular receptors (mechanosensors). How does the microenvironment, framed by the microfibril scaffold and populated by latent
growth factors, work? We must await future investigations for the molecular and cellular mechanisms that will answer this question. However, today we can appreciate the importance of the
fibrillin microfibril niche as a contextual environment for
growth factor signaling and potentially for mechanosensation.