Isabell Smyrek

Mammary gland development

The mammary gland is a highly dynamic organ, which not only underlies embryonic developmental processes but also postnatal modifications. The rodent mammary gland shares similarities with the human mammary gland. Therefore, and because of its dynamic changes in cell composition and function, the studies in rodents serve as a good model to provide insights into normal developmental processes as well as tumorigenesis (Russo and Russo 1996; Watson and Khaled 2008).

During pregnancy, the influence of mainly prolactin and placental lactogens induces ductal cells to proliferate into secretory alveolar cells (Hennighausen and Robinson 2005). These cells are capable of milk secretion. Furthermore, the blood-supply in the mammary gland increases by the formation of new capillaries in ultimate proximity to the individual alveoli. In late stages (day 19-21) of pregnancy, the alveoli make up the majority of the mammary gland. By day 18 of pregnancy, the secretory epithelial cells produce milk proteins and lipids (Richert, Schwertfeger et al. 2000). Milk secretion continues for about three weeks until weaning. Then, the mammary gland undergoes a complete remodelling process termed involution. This process can take up to two or three weeks, after which a status is reached comparable to a pre-pregnancy mature stage (Richert, Schwertfeger et al. 2000). The cycle of strong proliferation and cell differentiation during pregnancy, followed by apoptosis in involution can be repeated many times (Richert, Schwertfeger et al. 2000).

Figure 1: Anatomy of the mammary gland. Left: Volume rendering of mammary ducts that are embedded in the mammary fat pad. Middle: Single section of the mammary gland to illustrate the structure of the fat cells. Right: Surface rendering of mammary ducts. Microscope: mDSLM, Illumination objective: 2.5x/0.06 CZ Epiplan-Neofluar, Detection objective: 10x/0.3 CZ N-Achroplan, Scale bar: 100 µm

AJAP1

The adherens junction protein shrew-1/AJAP1 was originally isolated from an endometriosis cell line, which became non-invasive in late passages. This gene product is alternatively spliced, thus different protein isoforms may exist. Shrew-1/AJAP1 is a transmembrane protein, modulating the internalisation of E-cadherin induced by epidermal growth factor (EGF). Based on this knowledge, it is assumed that shrew-1/AJAP1 is mainly functional in tissues underlying remodelling processes, including changes in the dynamics of adherens junction. The mouse mammary gland provides a model system, in which these processes are abundant.We focus on the different shrew-1/AJAP1 isoforms and their function in the developing mammary gland. Biochemical methods as well as fluorescence microscopy are the tools for the research. With this work we hope to get insight into the functions of shrew-1 in the developing mammary gland and thereby understanding the dynamics of cell adhesion in these processes.

Autophagy in mammary gland development

Mammary involution results in loss of the major portion of secretory cells and degradation of the extracellular matrix. (Quarrie, Addey et al. 1996). Generally, it is distinguishable in two phases, of which the first is reversible. When pups are removed from the mother during lactation but returned within a certain time span, involution process can be halted. However, after a certain time, the remodelling process becomes irreversible. However, it is not understood how mammary gland involution is induced. One hypothesis is that milk stasis causes strain on alveolar cells inducing mechanotransduction, leading to increased autophagy, and finally initiation of involution. In our work, we focus on the development of internal forces and autophagy during the process of involution.

References

Hennighausen, L. and G. W. Robinson (2005). "Information networks in the mammary gland." Nature reviews. Molecular cell biology 6(9): 715-725.

Quarrie, L. H., C. V. P. Addey, et al. (1996). "Programmed Cell Death during Mammary Tissue Involution induced by Weaning, Litter Removal, and Milk Stasis." Journal of cellular physiology 168: 559-569.

Richert, M., K. L. Schwertfeger, et al. (2000). "An Atlas of Mouse Mammary Gland Development." Journal of mammary gland biology and neoplasia 5(2): 227-241.

Russo, I. H. and J. Russo (1996). "Mammary Gland Neoplasia in Long-Term Rodent Studies." Environmental health perspectives 104(9): 938-967.

Watson, C. J. and W. T. Khaled (2008). "Mammary development in the embryo and adult: a journey of morphogenesis and commitment." Development 135(6): 995-1003.