Immunolocalization of latent transforming growth factor-beta binding protein-1 (LTBP1) during mouse development: possible roles in epithelial and mesenchymal cytodifferentiation.

Latent transforming growth factor-beta binding protein-1 (LTBP1) is a member of the fibrillin family; it is a glycoprotein of more than 190 kDa that is characterized by its possession of 16-18 epidermal growth factor-like motifs and 8 cysteine residues. The secretion of transforming growth factor-beta involves its release from cells in a large latent complex containing LTBP1, a latency-associated peptide, and the mature region of the growth factor. Using a polyclonal antibody specific for LTBP1 (Ab39), we examined the immunohistochemical localization of this molecule during mouse embryogenesis between 8.5 and 13.5 embryonic days. An extracellular fibrillar structure containing LTBP1 was found in both the basement membrane of epithelia and mesenchymal tissue in which extensive tissue remodeling is carried out. Immunoelectron microscopy revealed Ab39 immunoreactivity on a 5- to 10-nm microfibrillar component of these basement membranes as well as in mesenchymal tissue. These results suggest that LTBP1 is one of the extracellular microfibrillar components of the basement membrane and of mesenchymal tissue, and that it may play an important role in the regulation of developmental phenomena involved in epithelial-mesenchymal interaction and epithelial differentiation, processes in which transforming growth factor-beta is required for the control of cellular differentiation.