Research – Developmental Biology and Stem Cell Regulation

Our Research


The hair follicle has become an important model system to study developmental processes, stem cell regulation and tissue morphogenesis for several reasons. First, it provides an excellent system to explore developmental mechanisms used to modify the same basic toolbox of interactions to regulate different developmental processes and to obtain distinct developmental outcomes. For example, epithelial-mesenchymal interactions in the embryo set up the scene for hair follicle specification and formation, and subsequently those same interactions are redeployed to execute the hair cycle in the adult. Second, the hair follicle provides an accessible system to study stem cells and their interactions with the immediate environment, often called the niche. As hair follicles undergo cycles of growth, destruction, quiescence and regeneration, different stem cell populations with distinct properties are required to repetitively execute these cycles. For this, the niche must provide and construct a unique milieu to regulate stem cell activity. Third, the hair follicle allows the study of development from the perspectives of multiple biological processes. The transitions between the different phases of the hair cycle involve dramatic morphological alterations and therefore require the coordination of multiple biological processes such as proliferation, apoptosis, cell migration, cellular communication and signal transduction.

 

Hair follicle formation

Hair follicle formation occurs during embryogenesis. At embryonic stage E13, the naïve embryonic skin is composed of two compartments: the epidermis with its monolayer of epithelial cells called keratinocytes and the dermis or mesenchyme with its unorganized dermal fibroblasts. Despite the basal membrane that physically separates the epidermis from the mesenchyme, epithelial-mesenchymal interactions pattern the epidermis to specify the location of hair follicles and segregate them from the interfollicular skin at the molecular level. Once the location is specified, hair placodes are formed. Placode formation represents the first morphological change in which follicular keratinocytes are re-shaped into columnar cells. While keratinocytes in the placode undergo proliferation to form the hair germ, signals generated by the placode instruct the underlying dermal fibroblasts to aggregate and form the dermal condensate. The latter plays an important role as an organizing center for subsequent developmental stages. It provides cues that enhance the proliferation rate of follicular keratinocytes and direct the growth of the follicle deep into the dermis. In the process of downgrowth, keratinocytes engulf the dermal condensate. This engulfment marks the formation of the dermal papilla, which further interacts with the surrounding keratinocytes to orchestrate and form the complex three-dimensional structures of the mature hair follicle with the hair shaft in the center.