Changes in expression of the lysosomal membrane glycoprotein, LAMP-1 in interdigital regions during embryonic mouse limb development, in vivo and in vitro.

Syndactyly, a failure of the digits to separate into individual units, affects about 8 to 9 per 1000 newborns and results from an aberration of the normal development of the interdigital tissues. Limb digit separation is the result of programmed cell death (apoptosis). Lysosomes play a role in the process of cell self-destruction.

In vitro model of syndactyly replicates the morphologic features observed in vivo.

Syndactyly is a common congenital hand anomaly that may occur after exposure to teratogens. We have developed an in vitro model of syndactyly to investigate the molecular mechanisms underlying this malformation of digit development. Retinoic acid, which regulates pattern formation in vertebrate limb development and is associated with teratogenic malformations, was used in the development of this syndactyly model system.

Mesenchymal commitment to digital joint formation.

Temporal and spatial commitment of in vivo and in vitro mammalian digital joint development were characterized in a murine model. Alcian blue and alizarin red staining were used to label proteoglycans of cartilage matrix and mineralized matrix in both whole mounts and histological sections. Mesenchymal differentiation toward a joint fate was identified by a lack of matrix deposition in islands of joint precursor cells between phalangeal precursors, and localized lysosomal enzyme activity was later demonstrated in these regions during formation of the joint cavity.

Human endothelial cells are defective in diabetic vascular disease.

Diabetic vascular disease is characterized pathologically by endothelial cell (EC) hyperplasia and basement membrane (BM) thickening. One key question regarding the pathogenesis of diabetic vascular disease is whether the EC or BM or both are primarily defective and responsible for these pathological changes. Previous studies, which took the approach of creating artificial diabetic conditions, have been inconclusive.

Interdigital soft tissue separation induced by retinoic acid in mouse limbs cultured in vitro.

The temporal pattern of separation of the soft tissue between mouse digits was examined in an organ culture model system. Mouse limbs of different gestational age were cultured in vitro and the pattern of separation of the digits characterized. By gestational day 12.