The purpose of this study was to provide a comprehensive and sequential account of the differentiation of the dermis in one body region in a mammalian species. A histological, histochemical, and ultrastructural study was made of each cellular and matrix component of the dermis of the upper lip of the mouse during prenatal development. On the basis of these observations, the development of the dermis was divided into four phases: I) undifferentiated mesenchyme (12, 13 days), II) cell differentiation (14, 15 days), III) dynamic transition (16 days), and IV) matrix differentiation (beginning at 17 days). The first phase was marked by a decrease in the cell density but no change in the ultrastructure of the undifferentiated mesenchyme cells. The second phase began with the cytodifferentiation of the mesenchyme cells and was characterized by the appearance of new cell types in the dermis (immature fibroblasts, mast cells, myoblasts, and cells of indeterminate type). During phase III the dermis was undergoing rapid change. Fibroblasts became fully differentiated, mast cell density reached a sharp peak, there was a marked increase in the number of collagen fibrils in the dermal matrix and the first collagen fibers were observed, and changes occurred in the pattern of proteoglycan synthesis. Aggregations of vesicles appeared to be extruded from cytoplasmic blebs on the fibroblasts in large quantities at this time. Further differentiation of the dermal intercellular matrix occurred during the fourth phase, which continued after birth, as more collagen was laid down to form the connective tissue stroma.
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