The mammary gland is a complex organ, composed of different cell types including the mammary epithelial cells (MEC) which synthesize and secrete milk. During mammary development, which continues throughout the life of female individuals, the MEC goes through different stages of differentiation. During pregnancy, the MEC will switch from a low differentiation stage associated with high proliferation potency to a highly differentiated stage associated with milk production and secretion. This highly differentiated stage is maintained throughout lactation. At the end of lactation, the mammary tissue involutes and the few MEC which then form the tissue are in a low differentiation state. They can evolve again through a new cycle of pregnancy and lactation. Each of these steps is finely tuned by a large number of endocrine and paracrine factors which act in concert within epithelial-stroma cell interactions.
Research conducted by the national and international communities on livestock animal models, deals mainly with lactation, control of milk production and milk composition. Selection programs aiming at improving milk production rely on quantitative data (milk quantity, protein yield, etc.) and qualitative data (protein and lipid composition of milk, etc.), but they do not take into account mammary development. However, mammary development is the subject of many studies relating to the understanding of the mechanisms of breast cancer and development of efficient therapeutics. Nevertheless, only a few teams are working on the mechanisms involved in normal mammary gland development, in particular during the cycles of cell proliferation, differentiation (associated with the secretion phenotype) and dedifferentiation. Furthermore, up to now projects that investigate the alteration of mammary development in relation with the environment remain scarce.
These questions are the bases of the GFP-GM project, which will focus on biological mechanisms involved in:
- The maintenance of each of the different stages of development (proliferation, differentiation, dedifferentiation).
- The transition from one stage to the other, in particular from a non-polarized to a polarized/non-secreting and then to a polarized/secreting phenotype.
- The molecular mechanisms underlying milk secretion and their regulation.
The MEC will be studied within the mammary tissue, in the animal and ex vivo. The role of myoepithelial cells, of the extracellular matrix and adipose tissue will be considered.
Key mechanisms will be selected after differential analyses between physiological stages (pregnancy, lactation, involution, etc.), between species (mouse, rabbit, ruminants), taking into account the genetic variability. Moreover, the influence of the environment (nutrition, livestock systems, pollution) on the mammary gland at different stages of development and during the transition periods will be characterized.
Our competences will allow integrative projects that require:
- Knowledge on cell physiology, genetics and epigenetics.
- Characterization of the MEC and other mammary tissue components by using different biological models (from the animal to the isolated MEC in cell culture).
- Understanding of molecular mechanisms underlying phenotypes observed in domestic animals, using mouse models and transgenesis.