Wnt signaling in skin organogenesis

Abstract

While serving as the interface between an organism and its environment, the skin also can elaborate a wide range of skin appendages to service specific purposes in a region-specific fashion. As in other organs, Wnt signaling plays a key role in regulating the proliferation, differentiation and motility of skin cells during their morphogenesis. Here I will review some of the recent work that has been done on skin organogenesis. I will cover dermis formation, the development of skin appendages, cycling of appendages in the adult, stem cell regulation, patterning, orientation, regional specificity and modulation by sex hormone nuclear receptors. I will also cover their roles in wound healing, hair regeneration and skin related diseases. It appears that Wnt signaling plays essential but distinct roles in different hierarchical levels of morphogenesis and organogenesis. Many of these areas have not yet been fully explored but are certainly promising areas of future research.The integument forms the interface between an organism and its environment. 1,2 As such it protects against dehydration, infection, temperature extremes, etc while providing a means for display, camouflage and other functions. 3 The skin can elaborate remarkable structural diversity producing specialized functions in a region-specific fashion to provide organisms with a selective advantage. For example, the development of feathers led to the acquisition of flight in birds and the formation of mammary glands enabled mammals to nurse their young. 4 The advantage of these evolutionary developments can be seen by the number of birds and mammals present today.Skin appendages, such as skin, hairs, feathers, scales, glands and teeth grow from the epithelium as a result of epithelial-mesenchymal interactions, 5 largely in response to common molecular signals with slight variations in their placement and timing during tissue morphogenesis. 6 Theoretically, stem cells are totipotent and progressively can be guided toward their specific fates by exposure to specific regulatory signals. The juxtaposition of molecular signals or lack thereof may have a tremendous impact on cell fate decisions. Hence, the difference between skin appendages is due to the topological arrangement of the epithelia during developmental processes. These are presumably regulated by adhesion molecules whose expression is controlled by signaling molecules as well as by physical constraints.Hairs and feathers are attractive model systems for experimental research because of their ability for seasonal or periodic renewal. Obviously not all hairs or feathers are replaced at one time or birds would lose all of their feathers at once and fall from the sky in midflight; rather hairs and feathers are replaced over a period of time in a wave-like pattern. 7 Yet this cycling behavior enables thousands of entirely new organs to be regenerated again and again throughout these animal's lives. Hairs and feathers demonstrate an incredible diversity of forms arising in different locations over the bod...

Wnt signaling induces epithelial differentiation during cutaneous wound healing

“…24 In the epithelium, Wnt 10b protein can be detected in migrating epithelial cells up to 3 d after wounding, while Wnt 4, 5a, and 10b localize to hair follicles. 25 Wnt 2a and 4 are expressed in the dermis, although reports vary with respect to the time-course of their expression (range: 30 h -7 d after wounding). It appears that Wnt signaling, through its ability to activate stem cells with induction of their self-renewal and proliferation, serves as a positive stimulus for wound repair.…”

Cutaneous Retinoic Acid Levels Determine Hair Follicle Development and Downgrowth

“…An essential pathway in hf development that we show to be affected in these RA excess mouse models is the Wnt signaling pathway (34,35). The role of Wnt signaling in placode and dermal condensate formation, hair shaft differentiation, and hair cycling has been established (35).…”

Deletion of mouse Porcn blocks Wnt ligand secretion and reveals an ectodermal etiology of human focal dermal hypoplasia/Goltz syndrome

“…FDH is commonly associated with localized defects in ectodermal appendages, such as hair, teeth, and nails (20), the development of which requires canonical Wnt signaling (41,42). Our efforts to study postnatal development of these tissues were frustrated by perinatal lethality, because several litters produced only a single viable but runted Porcn Δ/+ pup.…”