The dermal papilla (DP) cells of the hair follicle are permanent repository for epithelial progenitor cells that regenerate the hair follicle and generate the hair shaft. In this session, I will review experiments that revealed the importance of the DP cells (DPCs) in regulating the hair follicle regeneration and the hair growth cycles. I. DPCs in hair morphogenesis · Epidermal placode recruits cells from the underlying dermis · Dermal condensate: a local increase in dermal cell density beneath the epidermal placode · Active signaling between dermal condensate and placode stabilizes both populations and drives further development of the hair peg · Dermal condensate becomes the DP as it further compacts and is engulfed by the growing hair peg · DP act as the progenitor population that produces the inner root sheath (IRS) and hair shaft · At the end of the growth phase, the progenitor population adjacent the DPCs either differentiate or die · The hair shaft and IRS are drawn upward to the permanent portion of the follicle · Secondary germ: compact ball shaped DPCs which located at the base of resting follicle · Start of a new anagen phase: DPCs becomes less compact and the subsequent regeneration of the lower follicle is quite similar to initial morphogenesis · Throughout the hair cycle, the DP is well positioned to provide inductive signals that guide the activity of the cells that generate and regenerate the follicle · DPCs serve as the physical niche for progenitor cells II. DPCs as a regulator of hair growth environment · DPCs are dynamic regulator of hair follicle · Various types of gene expression of DPCs indicate that DPCs are source of diffusible signals that influence follicular epithelium · Implantation of DP was sufficient to restore regeneration · The role of the mesenchyme in directing morphology of the hair produced is maintained in the mature DPCs III. Anagen initiation · DPCs send signals to the stem cells of the follicular bulge to initiate a new anagen phase · Activation of the keratinocytes adjacent the DPCs is the first step of anagen initiation · DPCs expresse Wnts, FGFs, Noggin and R-spondins all of which can promote follicle growth and contribute to initiating follicular regeneration · Regeneration of the follicle accompany initial activation of signaling between mesenchyme and epithelium · β-catenin gene in DPCs is essential for the initiation of anagen -β-catenin gene lacking in the DP enter the telogen phase, fail to reenter anagen · Reduced cell number of DP induce delayed anagen initiation · Importance of macroenvironmental factor - signals from adjacent follicles - signals from other cell types in the skin - hormonal signals generated outside the skin IV. Maintenance of DP size · DPCs population in a follicle is not fixed - decrease number during telogen phase, but restore at anagen · Healthy and normal-sized epithelial compartment can either recruit new cells or sustain the proliferation of existing DPCs to regenerate its niche · The source of additional DPCs during regeneration after damage has not been characterized