Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis

Keymeulen, Alexandra Van; Mascré, Guilhem; Youseff, Khalil Kass; Harel, Itamar; Michaux, Cindy; Geest, Natalie De; Szpalski, Caroline; Achouri, Younès; Bloch, Wilhelm; Hassan, Bassem A.; Blanpain, Cédric

doi:10.1083/jcb.200907080

Cited by 234 publications

(192 citation statements)

References 40 publications

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“…Our time course data confirm previous analyses for these structures (2,10,11,13,21,28), which demonstrated that follicles, sensory afferents, and Merkel cell clusters develop prenatally, whereas APMs and sebaceous glands develop postnatally (Fig. 7).…”

Section: Developmental Time Course and Patterns Of Fz6 Expression In supporting

confidence: 80%

Responses of hair follicle–associated structures to loss of planar cell polarity signaling

Chang

Nathans

2013

Proc. Natl. Acad. Sci. U.S.A.

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The mammalian hair follicle unit consists of a central follicle and a series of associated structures: sebaceous glands, arrector pili muscles, Merkel cells, and sensory nerve endings. The architecture of this multicellular structure is highly polarized with respect to the body axes. Previous work has implicated Frizzled6 (Fz6)-mediated planar cell polarity (PCP) signaling in the initial specification of hair follicle orientation. Here we investigate the origin of polarity information among structures within the hair follicle unit. Merkel cell clusters appear to have direct access to Fz6-based polarity information, and they lose polarity in the absence of Fz6. By contrast, the other follicle-associated structures likely derive some or all of their polarity cues from hair follicles, and as a result, their orientations closely match that of their associated follicle. These experiments reveal the interplay between global and local sources of polarity information for coordinating the spatial arrangement of diverse multicellular structures. They also highlight the utility of mammalian skin as a system for quantitative analyses of biological polarity.

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Section: Developmental Time Course and Patterns Of Fz6 Expression In supporting

confidence: 80%

Responses of hair follicle–associated structures to loss of planar cell polarity signaling

Chang

Nathans

2013

Proc. Natl. Acad. Sci. U.S.A.

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“…This idea was initially supported by cell lineagetracing studies that identified Wnt1-expressing neural crest stem cells as the site of Merkel cell origin (Szeder et al, 2003). However, multiple recent reports comparing murine lineage-tracing models using a Wnt1 or cytokeratin 14 (Krt14 or K14) Cre driver indicate that Merkel cells are derived from the proliferative keratinocyte (Krt14-expressing) layer of skin and not the neural crest (Morrison et al, 2009;Van Keymeulen et al, 2009). In support of these findings, conditional deletion of the atonal helixloop-helix transcription factor Atoh1 in K14-Cre mice was shown to abolish Merkel cell development, whereas in Wnt1-Cre mice it had no effect on the development or maintenance of Merkel cells.…”

Section: Introductionmentioning

confidence: 81%

Identification of epidermal progenitors for the Merkel cell lineage

et al. 2010

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Epithelial stem cells in adult mammalian skin are known to maintain epidermal, follicular and sebaceous lineages during homeostasis. Recently, Merkel cell mechanoreceptors were identified as a fourth lineage derived from the proliferative layer of murine skin epithelium; however, the location of the stem or progenitor population for Merkel cells remains unknown. Here, we have identified a previously undescribed population of epidermal progenitors that reside in the touch domes of hairy skin, termed touch dome progenitor cells (TDPCs). TDPCs are epithelial keratinocytes and are distinguished by their unique co-expression of α6 integrin, Sca1 and CD200 surface proteins. TDPCs exhibit bipotent progenitor behavior as they give rise to both squamous and neuroendocrine epidermal lineages, whereas the remainder of the α6+ Sca1+ CD200– epidermis does not give rise to Merkel cells. Finally, TDPCs possess a unique transcript profile that appears to be enforced by the juxtaposition of TDPCs with Merkel cells within the touch dome niche.

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“…MCs express intermediate filaments of simple epithelia, such as K8, K18, and K20, as well as neuropeptides, proneural transcription factors, and components of presynaptic machinery, suggesting that MCs arise from neural crest cells. However, lineage-tracing experiments using epidermal and neural crest -specific promoters unambiguously show that MCs arise from epidermal cells by a mechanism that requires Atoh1 expression (Morrison et al 2009;Van Keymeulen et al 2009). …”

Section: Functional Anatomy Of the Skin Epidermismentioning

confidence: 99%

Development and Homeostasis of the Skin Epidermis

Sotiropoulou

Blanpain

2012

Cold Spring Harbor Perspectives in Biology

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SUMMARYThe skin epidermis is a stratified epithelium that forms a barrier that protects animals from dehydration, mechanical stress, and infections. The epidermis encompasses different appendages, such as the hair follicle (HF), the sebaceous gland (SG), the sweat gland, and the touch dome, that are essential for thermoregulation, sensing the environment, and influencing social behavior. The epidermis undergoes a constant turnover and distinct stem cells (SCs) are responsible for the homeostasis of the different epidermal compartments. Deregulation of the signaling pathways controlling the balance between renewal and differentiation often leads to cancer formation.

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Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis

Abstract: Lineage-tracing experiments show that the origin of specialized mechanosensory Merkel cells in the skin is epidermal progenitors, not the neural crest.

Cited by 234 publications

References 40 publications

Responses of hair follicle–associated structures to loss of planar cell polarity signaling

Responses of hair follicle–associated structures to loss of planar cell polarity signaling

Identification of epidermal progenitors for the Merkel cell lineage

Development and Homeostasis of the Skin Epidermis

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