Dermal fibroblasts are required for structural integrity of the skin and for hair follicle development. Uniform Wnt signaling activity is present in dermal fibroblast precursors preceding hair follicle initiation, but the functional requirement of dermal Wnt signaling at early stages of skin differentiation and patterning remains largely uncharacterized. We show in mice that epidermal Wnt ligands are required for uniform dermal Wnt signaling/β-catenin activity and regulate fibroblast cell proliferation and initiation of hair follicle placodes. In the absence of dermal Wnt signaling/β-catenin activity, patterned upregulation of epidermal β-catenin activity and Edar expression are absent. Conversely, forced activation of β-catenin signaling leads to the formation of thickened dermis, enlarged epidermal placodes and dermal condensates that result in prematurely differentiated enlarged hair follicles. These data reveal functional roles for dermal Wnt signaling/β-catenin in fibroblast proliferation and in the epidermal hair follicle initiation program.

The dermis promotes the development and maintains the functional components of skin, such as hair follicles, sweat glands, nerves and blood vessels. The dermis is also crucial for wound healing and homeostasis of the skin. The dermis originates from the somites, the lateral plate mesoderm and the cranial neural crest. Despite the importance of the dermis in the structural and functional integrity of the skin, genetic analysis of dermal development in different parts of the embryo is incomplete. The signaling requirements for ventral dermal cell development have not been established in either the chick or the mammalian embryo. We have shown previously that Wnt signaling specifies the dorsal dermis from the somites. In this study, we demonstrate that Wnt/β-catenin signaling is necessary for the survival of early ventral dermal progenitors. In addition, we show that, at later stages,Wnt/β-catenin signaling is sufficient for ventral dermal cell specification. Consistent with the different origins of dorsal and ventral dermal cells, our results demonstrate both conserved and divergent roles ofβ-catenin/Wnt signaling in dermal development.

Wnt signaling is critical for proper development of the head and face in the mouse embryo, playing important roles in various aspects of craniofacial development ranging from axis formation to survival of cranial neural crest cells to patterning of the brain. The signaling requirements for the development of different cell lineages in the head and face are active areas of investigation. In this study, we use a recently developed TCF/Lef‐LacZ transgenic reporter mouse to characterize the expression of canonical Wnt signaling activity during craniofacial development. We present an atlas of representative sections to show embryonic craniofacial development. Our results demonstrate a pattern of sustained Wnt signaling reporter activity in most tissues which suggests sequential roles in craniofacial development. Developmental Dynamics 239:354–363, 2010.

Cranial dermis develops from cephalic mesoderm and neural crest cells, but what signal(s) specifies the dermal lineage is unclear. Using genetic tools to fate map and manipulate a cranial mesenchymal progenitor population in the supraorbital region, we show that the dermal progenitor cells beneath the surface ectoderm process canonical Wnt signaling at the time of specification. We show that Wnt signaling/β-catenin is absolutely required and sufficient for Dermo1 expression and dermal cell identity in the cranium. The absence of the Wnt signaling cue leads to formation of cartilage in craniofacial and ventral trunk regions at the expense of dermal and bone lineages. Dermo1 can be a direct transcription target and may mediate the functional role of Wnt signaling in dermal precursors. This study reveals a lineage-specific role of canonical Wnt signaling/β-catenin in promoting dermal cell fate in distinct precursor populations.