Fibulin-1 and fibulin-2 expression during organogenesis in the developing mouse embryo

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Abstract
Fibulin-1 and fibulin-2 are extracellular matrix proteins with unique structural features. We used in situ hybridization and immunofluorescence staining to examine the expression of fibulin-1 and fibulin-2 during mouse embryogenesis. Both fibulins have previously been shown to be deposited at sites where polarized cells convert into mesenchyme, during early stages of development of endocardial cushion tissue and in neural crest cells. By Northern blots we confirm that expression of fibulin-2 is particularly high in the developing and newborn heart. We also show that fibulin-2 mRNA and protein remained highly expressed during organogenesis in tissues derived from neural crest mesenchyme. In addition, a locally restricted expression pattern of fibulin-1 and fibulin-2 mRNA and protein at sites of epithelial-mesenchymal interactions was detected in two tissues, the developing tooth and hair follicles. In other tissues where epithelial-mesenchymal interactions occur, fibulin-1 mRNA and its corresponding protein were detected rather uniformly around mesenchymal cells, and no expression of fibulin-2 was noted. Fibulin-1 protein was located in some embryonic epithelial basement membranes. Fibulin-1 mRNA was also expressed in the epidermal layer of brain and in the mesenchyme of choroid plexus and the meninges which surround the spinal cord. Overall, fibulin-2 expression was much more limited than fibulin-1 expression. A very prominent expression of fibulin-2 was seen during early stages of chondrogenesis in all cartilages analyzed. These studies show that the differential expression of the fibulin family contributes to the formation of molecularly distinct extracellular matrices already during early developmental stages of a large number of tissues.