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Morphogenesis of the mammary gland and the role of keratin expression

The selective expression of keratin genes is highly tissue-specific, and antibodies to keratins have long been used as markers of differentiation in cell and developmental biology and in pathology applications. Antibodies to keratins can mark the progress of normal versus abnormal differentiation, can detect early apoptotic changes and may even identify stem cell-enriched tissue populations. A better understanding of the function of keratins has come from identifying links between keratin mutations and a wide range of tissue fragility disorders, which have shown that keratin intermediate filament proteins contribute physical resilience to epithelial tissues. The tissue specificity of keratins may thus reflect different requirements for stiffer or more plastic cells in particular organ sites. We re-examined the early development of the mammary gland to ask whether differences in the plasticity of cell compartments, proposed to result from expression of different keratins, may contribute to morphogenesis in development. If so, such physical differences might also be important in cancer metastasis. During early development, mouse mammary glands, like other epidermal appendages, first appear as thickenings of the ectoderm, which then expand to form solid buds of epithelial cells protruding into the mesenchyme. These buds then undergo substantial growth and remodeling. Many well-established signaling molecules are now known to play a role in epidermal appendage development, yet the physical changes that take place within the cells at these early stages, and which ultimately enable them to develop their functional tissue morphology, are still poorly understood. Using immunohistochemistry on mouse mammary gland precursors between days 12 and 19 of gestation, we mapped the sequential changes in expression of keratins and some other key structural proteins. Compartmentalization of keratin expression was observed to divide the mammary gland rudiment into a number of different zones. The subsequent fate of these zones suggests that the specific expression of keratins and other structural proteins may indeed predict the functional capacity of cell populations in tissues.

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Aldahmash, A., Lunny, D. & Lane, B. Morphogenesis of the mammary gland and the role of keratin expression. Breast Cancer Res 7 (Suppl 2), P3.09 (2005).

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