Morphoregulation and cycling of ectodermal organs

UnrestrictedEctodermal organs are produced through the series of epithelial-mesenchymal interactions followed by topological transformation of the otherwise flat ectodermal layer. Fundamental signaling pathways regulate development of ectodermal organs. Fine tuning of the organ's size and shape during development is achieved by mild spatial-temporal changes of signaling pathway activity rather than on-off switches. In my work I have investigated the extent of morphoregulatory activities of Bmp signaling pathway. I have modulated normal Bmp signaling by overexpressing of Bmp antagonist noggin under keratin 14 promoter in K14-noggin mice. I have shown that changes in Bmp pathway activity can alter various ectodermal organs at different developmental stages: induction (increased number of pelage hair follicles, formation of compound vibrissa follicles, claw agenesis, transdifferentiation of sweat glands into hair follicles etc.), morphogenesis (defect of eyelids opening, enlargement of external genitalia etc.) or differentiation (incomplete differentiation of claw plates, retarded differentiation of hairy spines). I have further shown that in morphologically complex teeth, Bmp pathway regulates all of the above stages of development.; Furthermore, I have identified a new physiological mechanism of hair cycle control. I have shown that rather than being an autonomous intra-follicular event, the critical telogen-anagen transition during the hair cycle is largely regulated by signals originating from the extra-follicular environment and neighboring hair follicles. I have conclusively identified skin-wide changes in Bmp signaling activity as the major regulatory factor of telogen-anagen transition in large populations of hair follicles. My findings allow to view the hair cycle in the content of the microenvironment surrounding the hair follicle. They allow us to explain how hair follicles make decisions on hair cycle progression by "listening" to other follicles and inter-follicular signaling centers and how multiple hair follicles can coordinate their hair cycles to form macroscopic growth patterns. My findings open new area for hair cycle control studies that takes an integrative approach and views hair follicles in relation to the surrounding stroma and neighboring follicles. My work proves morphoregulation hypothesis by showing how mild spatial-temporal changes in a single fundamental signaling pathway can modulate all stages of development of multiple ectodermal organs