Keratinocyte Growth Factor Promotes Melanosome Transfer to Keratinocytes

Cardinali, Giorgia; Ceccarelli, Simona; Kovacs, Daniela; Aspite, Nicaela; Lotti, Lavinia Vittoria; Torrisi, Maria Rosaria; Picardo, Mauro

doi:10.1111/j.0022-202x.2005.23929.x

Cited by 115 publications

(148 citation statements)

References 36 publications

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“…The activation of Rac and Cdc42, but not RhoA, by DOCK7 suggests a possible mechanism for the pigmentation phenotypes displayed by Dock7 m/m and Dock7 mnlt/mnlt mice. Both Rho and Rac family members contribute to the formation of melanocyte dendrites that are necessary for the transfer of melanin from melanocytes to adjacent keratinocytes (12,13). Indeed, numerous studies indicate that dendrite formation in neural cells is controlled by a balance between Rac and Rho activities, with Rho activation promoting neurite retraction and Rac activation promoting neurite outgrowth (13,31,32,33).…”

Section: Discussionmentioning

confidence: 99%

Mice with mutations of Dock7 have generalized hypopigmentation and white-spotting but show normal neurological function

Blasius¹,

Brandl²,

Crozat³

et al. 2009

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

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The classical recessive coat color mutation misty (m) arose spontaneously on the DBA/J background and causes generalized hypopigmentation and localized white-spotting in mice, with a lack of pigment on the belly, tail tip, and paws. Here we describe moonlight (mnlt), a second hypopigmentation and white-spotting mutation identified on the C57BL/6J background, which yields a phenotypic copy of m/m coat color traits. We demonstrate that the 2 mutations are allelic. m/m and mnlt/mnlt phenotypes both result from mutations that truncate the dedicator of cytokinesis 7 protein (DOCK7), a widely expressed Rho family guanine nucleotide exchange factor. Although Dock7 is transcribed at high levels in the developing brain and has been implicated in both axon development and myelination by in vitro studies, we find no requirement for DOCK7 in neurobehavioral function in vivo. However, DOCK7 has non-redundant role(s) related to the distribution and function of dermal and follicular melanocytes.misty ͉ melanocyte ͉ coat color ͉ guanine nucleotide exchange factor ͉ rho GTPase

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Section: Discussionmentioning

confidence: 99%

Mice with mutations of Dock7 have generalized hypopigmentation and white-spotting but show normal neurological function

Blasius¹,

Brandl²,

Crozat³

et al. 2009

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

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“…FGF7-and FGF10 mRNA expression peaks at the anagen stage V. 70 FGF7 is also involved in skin pigmentation where it promotes melanosome transfer to keratinocytes in a FGFR2-dependent process thereby regulating both the early steps of uptake and the intracellular trafficing of the phagosomes. 71 Recently, acne arising strictly within a preexisting keratinocytic epidermal nevus during puberty, has been reported. 72 …”

Section: Animal Model Of Apert Syndromementioning

confidence: 99%

Role of FGFR2-signaling in the pathogenesis of acne

Melnik

2009

Dermato-Endocrinology

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It is the purpose of this review to extend our understanding of the fibroblast growth factor (FGF) receptor-2b-signaling network in the pathogenesis of acne. A new concept of the role of FGFR2b-signaling in dermal-epithelial interaction for skin appendage formation, pilosebaceous follicle homeostasis, comedogenesis, sebaceous gland proliferation and lipogenesis is presented. The FGFR2-gain-of-function mutations in Apert syndrome and unilateral acneiform nevus are most helpful model diseases pointing the way to androgen-dependent dermalepithelial FGFR2-signaling in acne. Androgen-mediated upregulation of FGFR2b-signaling in acne-prone skin appears to be involved in the pathogenesis of acne vulgaris. In organotypic skin cultures, keratinocyte-derived interleukin-1α stimulated fibroblasts to secrete FGF7 which stimulated FGFR2b-mediated keratinocyte proliferation. Postnatal deletion of FGFR2b in mice resulted in severe sebaceous gland atrophy. The importance of FGFR2b in sebaceous gland physiology is further supported by the mode of action of anti-acne agents which have been proposed to attenuate FGFR2b-signaling. Downregulation of FGFR2b-signaling by isotretinoin explains its therapeutic effect in acne. Downregulation of FGFR2b-signaling during the first trimester of pregnancy disturbs branched morphogenesis and explains retinoid embryotoxicity. Insulin-like growth factor-1 (IGF-1), the mediator of growth hormone during puberty, intracts with androgen-dependent FGFR2b-signaling and links androgen-and FGF-mediated signal transduction important in sebaceous gland homeostasis. The search for a follicular defect in the dermalepithelial regulation of growth factor-signaling in acne-prone skin appears to be a most promising approach to clarify the pathogenesis of acne.

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“…Phagocytosis of pigment granules by epidermal keratinocytes has been proposed to be an important mechanism of pigment transfer from melanocytes to keratinocytes (Cardinali et al, 2005). To analyze the phagocytic capacity of keratinocytes with inhibited Rac1 activity, we determined the uptake of fluorescently labeled polystyrene microparticles (fluorospheres) into primary keratinocytes, as described previously (Cardinali et al, 2005).…”

Section: Disturbance Of Pigment Granule Size and Deposition In Rescuementioning

confidence: 99%

A function for Rac1 in the terminal differentiation and pigmentation of hair

Behrendt

Klatte

Pofahl

et al. 2012

Journal of Cell Science

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SummaryThe small GTPase Rac1 is ubiquitously expressed in proliferating and differentiating layers of the epidermis and hair follicles. Previously, Rac1 was shown to regulate stem cell behaviour in these compartments. We have asked whether Rac1 has, in addition, a specific, stem-cell-independent function in the regulation of terminal hair follicle differentiation. To address this, we have expressed a constitutively active mutant of Rac1, L61Rac1, only in the basal epidermal layer and outer root sheath of mice possessing an epidermisspecific deletion of endogenous Rac1, which experience severe hair loss. The resulting 'rescue' mice exhibited a hair coat throughout their lives. Therefore, expression of Rac1 activity in the keratin-14-positive compartment of the skin is sufficient for the formation of hair follicles and hair in normal quantities. The quality of hair formed in rescue mice was, however, not normal. Rescue mice showed a grey, dull hair coat, whereas that of wild-type and L61Rac1-transgenic mice was black and shiny. Hair analysis in rescue mice revealed altered structures of the hair shaft and the cuticle and disturbed organization of medulla cells and pigment distribution. Disorganization of medulla cells correlates with the absence of cortical, keratin-filled spikes that normally protrude from the cortex into the medulla. The desmosomal cadherin Dsc2, which normally decorates these protrusions, was found to be reduced or absent in the hair of rescue mice. Our study demonstrates regulatory functions for Rac1 in the formation of hair structure and pigmentation and thereby identifies, for the first time, a role for Rac1 in terminal differentiation.

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Keratinocyte Growth Factor Promotes Melanosome Transfer to Keratinocytes

Cited by 115 publications

References 36 publications

Mice with mutations of Dock7 have generalized hypopigmentation and white-spotting but show normal neurological function

Mice with mutations of Dock7 have generalized hypopigmentation and white-spotting but show normal neurological function

Role of FGFR2-signaling in the pathogenesis of acne

A function for Rac1 in the terminal differentiation and pigmentation of hair

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