Versican is a critical extracellular matrix protein in lung and brain during embryonic development in the mouse (1046.9)

Abstract

Versican, a chondroitin sulfate proteoglycan and a component of the extracellular matrix, is associated with fatal cardiac malformations if absent during embryonic development and is increased with injury in adult tissues. Changes in versican gene expression and accumulation have not been examined comprehensively in the lung and brain during mid to late gestation in the mouse. The objective of this work was to determine if versican accumulation and degradation change during lung and brain embryogenesis. Quantitative PCR and immunohistochemistry were used to measure versican expression, accumulation and degradation in the lung, brain, heart and liver of C57Bl/6 mice for five consecutive days during embryonic development. Consistent with previous reports, we found that total versican gene expression was higher in embryonic tissues when compared to adults and the highest total versican gene expression in embryos occurred at embryonic day 13.5 (E13.5). At E15.5, versican gene expression was lowest in the liver, highest in the brain, and intermediate in the heart and lung. There was differential expression of versican isoforms, with V0, V1, and V2 isoforms increased in the brain but only V0 and V1 isoforms increased in the lung. Versican expression in the lung peaked at E13.5, at which time there was strong versican immunoreactivity in the interstitium and airway basement membrane but little accumulation in airway epithelial cells. In the brain, immunoreactivity was strongest in the roof of the hind brain and neopallial cortex and in the deeper white matter tracts, and at later gestational ages there was little accumulation in the developing choroid plexus and periventricular gray matter. During embryonic development of the lung and brain, we found areas of versican expression that colocalized with the expression of DPEAAE, a versican degradation product. These results suggest that versican plays an important role in embryogenesis of the lung and brain.Grant Funding Source: Supported by HL098067, RR030249