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Wnt5a is expressed in the developing dermal condensate in wild type but not in Shh-null mice embryos, indicating that Wnt5a is a target of Shh in hair follicle morphogenesis Reddy et al. Shh-null skin analysis showed that Shh is not a component of the first epithelial signal Schneider et al.

Hair Follicle

Dermal Smoothened smo loss of function results in loss of the dermal condensate and overexpression of Shh-dependent Noggin. This phenotype is partially rescued by the knockdown of noggin in the hair follicle by increasing the expression of epithelial shh Woo et al. Laminin mutants show developmental defects by E The peribulbar DS, which covers the outside of the hair follicle, contains mesenchymal cells that contribute to the maintenance and regeneration of the FDP Jahoda and Reynolds, ; Driskell et al. The FDP gene expression pattern is heterogeneous and depends on the hair follicle type.

It has been shown that Sox2 is expressed in all dermal papillae at E Sox2 distinct subpopulations express different sets of genes in addition to the FDP gene signature Driskell et al. FDP cells are not believed to divide, but during anagen the number of dermal cells in the dermal papillae increases, probably due to migration of cells from the DS Chi et al.

During anagen, FDP induces downward growth of the stem cells in the secondary hair germ. A quantitative analysis using the rodent vibrissa model indicated that the hair inductivity capacity of FDP cells is altered between early anagen and mid-anagen, being higher in the former, a phenomenon probably linked to the proliferative activity Iida et al.

Research Areas

Specific FDP markers which are upregulated during anagen in the adult mouse skin are the Corin serine protease and Sox-2 Driskell et al. The FDP is also a reservoir of multipotent stem cells Biernaskie et al. At least three different subpopulations of progenitor cells may be identified: i Sox-2 positive cells, which are associated with Wnt, BMP, and FGF signaling; ii Sox-2 negative cells, associated with Shh, Insulin Growth Factor IGF , Notch, and Integrin pathways; and iii skin-derived precursors SKPs , which may differentiate into adipocytes, smooth myocytes and neurons in vitro; they are believed to originate from Sox-2 positive cells, and in part from the neural crest Biernaskie et al.

The fact that cells isolated from different anatomical locations including the back skin derived from the dermomyotome display multipotent stem cell characteristics suggests that the hair follicle environment, rather than the embryonic origin, induces the generation of cells with the characteristics of neural crest derivatives Driskell et al. A comparative analysis between the mesenchymal stem cells MSCs isolated from FDP and DS and those isolated from bone marrow showed that these MCs have similar morphology and population doubling time and express the same cell surface biomarkers Hoogduijn et al.

Also, both cell populations had the capacity to differentiate into the same mesenchymal lineages osteoblasts, adipocytes, chondrocytes and myocytes at similar rates and extent of differentiation Hoogduijn et al. As a non-invasive source of progenitor cells, the dermal papilla and dermal sheath are viable and promising candidates for use in the clinic. Sebaceous glands are important in the maintenance of the hair, since absence of these glands was associated with scarring alopecia and doxorubicin-induced hair loss Al-Zaid et al.

  1. Localization of Myosin and Actin in the Pelage and Whisker Hair Follicles of Rat!
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The sebaceous glands are composed mainly of sebocytes, which are highly specialized epithelial cells that release their sebum content through a process that culminates in the rupture of the cell membrane and cellular extravasation known as holocrine secretion Frances and Niemann, The majority of sebaceous glands are an integral part of a pilosebaceous unit, although this structure can appear as an independent structure in mutant mice lacking hair follicles Mecklenburg et al.

The Sebaceous Gland SG , of ectodermal origin, develops late in embryogenesis in the upper portion of the HF, from the same lineage as that of keratinocytes. Nevertheless, Sox-9 ablation in the embryo led to failed SG formation, even though Sox-9 is not expressed in the SG lineage or in its resident precursors Nowak et al.

During homeostasis of adult mouse skin, Lrig1-positive cells contribute to the infundibulum and the sebaceous glands Jensen et al. Blimp1, a transcriptional repressor, was shown to be a marker of the early stage SG-residing progenitor cell linage. Loss of Blimp1 leads to elevated c -myc expression, augmented cell proliferation and SG hyperplasia, resulting in enhanced bulge stem cell activity Horsley et al. In addition, SG fails to develop in gamma-secretase null mice, in a mechanism dependent on Notch proteolysis Pan et al.

Inhibition of the Shh pathway selectively suppresses sebocyte development, whereas its activation leads to an increase in the size and number of SG Allen et al. On the other hand, Wnt pathway inhibition appears to be crucial for SG development, since Smad7 transgenic induction perturbed hair follicle morphogenesis and differentiation and accelerated SG morphogenesis Han et al. The Wnt pathway is also overexpressed in sebaceous gland carcinoma Erovic et al. Taken together, these findings show that SG development and maintenance involves a unique gene signature that interplays with the HF and FDP signaling pathways.

The skin constitutes a reservoir for adult stem cells of different embryonic origins. Skin stem cell populations reside in the adult hair follicle, sebaceous gland, dermis and epidermis; however, the origin of most of these stem cell populations is still unknown.


In this review we attempted to clarify the emergence, structure, markers and embryonic development of diverse populations of stem cells from the epidermis, dermis and related appendages such as the sebaceous gland and hair follicles. Further studies on skin stem cell specification and commitment are crucial for development of the knowledge of the dynamics of this tissue and for effective cell therapy protocols.

Sebaceous gland loss and inflammation in scarring alopecia: a potential role in pathogenesis. J Am Acad Dermatol. Hedgehog signaling regulates sebaceous gland development.

Hair follicle - Wikipedia

The American journal of pathology. WNT signals are required for the initiation of hair follicle development. Dev Cell. Stem cells in ectodermal development. J Mol Med Berl. Identification and localization of label-retaining cells in hamster epithelia. J Invest Dermatol. SKPs derive from hair follicle precursors and exhibit properties of adult dermal stem cells. Cell stem cell. Skin-derived precursors generate myelinating Schwann cells that promote remyelination and functional recovery after contusion spinal cord injury. J Neurosci. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in wholemounts of mouse epidermis.


Development Cambridge, England. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol. De novo production of dermal papilla cells during the anagen phase of the hair cycle. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Transcriptional control of epidermal specification and differentiation.

Curr Opin Genet Dev. Hair follicle dermal papilla cells at a glance. J Cell Sci. Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis. Clonal growth of dermal papilla cells in hydrogels reveals intrinsic differences between Sox2-positive and -negative cells in vitro and in vivo.

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  • 1. Introduction.
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  • Isolating a pure population of epidermal stem cells for use in tissue engineering. Experimental dermatology. Developmental cell.

    Pulling out a Hair Under the Microscope!

    Identification of novel target proteins in sebaceous gland carcinoma. Versican targeting by RNA interference suppresses aggregative growth of dermal papilla cells. Clinical and experimental dermatology. A dermal niche for multipotent adult skin-derived precursor cells. Nat Cell Biol. Stem cell dynamics in sebaceous gland morphogenesis in mouse skin. Developmental biology. Scratching the surface of skin development. Changes in keratin gene expression during terminal differentiation of the keratinocyte. Getting under the skin of epidermal morphogenesis.

    Nat Rev Genet. Laminin is an epithelial message promoting dermal papilla development and function during early hair morphogenesis. Genes Dev. Mechanisms of neural specification from embryonic stem cells. Curr Opin Neurobiol. Protein kinase C isoforms have differential roles in the regulation of human sebocyte biology. Smad7-induced beta-catenin degradation alters epidermal appendage development. Comparative characterization of hair follicle dermal stem cells and bone marrow mesenchymal stem cells.

    Stem cells and development. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Follicular epithelia and dermal papillae of mouse vibrissal follicles qualitatively change their hair-forming ability during anagen. Differentiation; research in biological diversity. Hair follicle dermal sheath cells: unsung participants in wound healing.