Hedgehog Signaling, Keratin 6 Induction, and Sebaceous Gland Morphogenesis

Gu, Li Hong

doi:10.2353/ajpath.2008.071089

Cited by 28 publications

(12 citation statements)

References 81 publications

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“…The latter finding suggests that reduced wax diester content in Fa2h Ϫ/Ϫ sebum is not caused by reduced expression of these enzymes but most likely results from inefficient diol synthesis caused by reduced fatty acid 2-hydroxylase activity. The keratin K6a, which is specifically expressed in the suprabasal layer of SG (30), was significantly up-regulated in Fa2h Ϫ/Ϫ mice, in line with sebocyte hyperproliferation (Table 2). Up-regulation of several sebocyte markers, Scd1, Scd3, and PPAR␥, was confirmed by quantitative real time RT-PCR (Fig.…”

Section: C Arrowhead) the Number Of Ki67-positive Cells Per Sg Wasmentioning

confidence: 74%

Normal Fur Development and Sebum Production Depends on Fatty Acid 2-Hydroxylase Expression in Sebaceous Glands

Maier

Meixner

Hartmann

et al. 2011

Journal of Biological Chemistry

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2-Hydroxylated fatty acid (HFA)-containing sphingolipids are abundant in mammalian skin and are believed to play a role in the formation of the epidermal barrier. Fatty acid 2-hydroxylase (FA2H), required for the synthesis of 2-hydroxylated sphingolipids in various organs, is highly expressed in skin, and previous in vitro studies demonstrated its role in the synthesis of HFA sphingolipids in human keratinocytes. Unexpectedly, however, mice deficient in FA2H did not show significant changes in their epidermal HFA sphingolipids. Expression of FA2H in murine skin was restricted to the sebaceous glands, where it was required for synthesis of 2-hydroxylated glucosylceramide and a fraction of type II wax diesters. Absence of FA2H resulted in hyperproliferation of sebocytes and enlarged sebaceous glands during hair follicle morphogenesis and anagen (active growth phase) in adult mice. This was accompanied by a significant up-regulation of the epidermal growth factor receptor ligand epigen in sebocytes. Loss of FA2H significantly altered the composition and physicochemical properties of sebum, which often blocked the hair canal, apparently causing a delay in the hair fiber exit. Furthermore, mice lacking FA2H displayed a cycling alopecia with hair loss in telogen. These results underline the importance of the sebaceous glands and suggest a role of specific sebaceous gland or sebum lipids, synthesized by FA2H, in the hair follicle homeostasis.

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Section: C Arrowhead) the Number Of Ki67-positive Cells Per Sg Wasmentioning

confidence: 74%

Normal Fur Development and Sebum Production Depends on Fatty Acid 2-Hydroxylase Expression in Sebaceous Glands

Maier

Meixner

Hartmann

et al. 2011

Journal of Biological Chemistry

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“…Interestingly, a transient increase in expression of marker molecules associated with SG lineage fate was seen at early stages of ectopic SG formation ( Figure 6F ). Blimp1 and K6a ( Gu and Coulombe, 2008 ) are upregulated throughout the process of ectopic SG formation, whereas expression of the lipid modifying enzyme Elovl3 ( Westerberg et al, 2004 ) is strongly elevated when the early steps of de novo SG formation are completed ( Figure 6F ). Previously, a recapitulation of the HF differentiation programme was seen in mouse models investigating the development of ectopic HFs ( Lo Celso et al, 2004 ; Silva-Vargas et al, 2005 ).…”

Section: Resultsmentioning

confidence: 99%

TCF/Lef1 activity controls establishment of diverse stem and progenitor cell compartments in mouse epidermis

Petersson

Brylka

Kraus

et al. 2011

EMBO J

101

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TCF/Lef1 activity controls establishment of diverse stem and progenitor cell compartments in mouse epidermisThis work investigates cell fate and lineages of hair follicles and sebaceous glands (SG) in the mouse epidermis. The combination of transgenic models with complementary tracing techniques provides unequivocal evidence for a direct contribution of bulge stem cells to the SG units as well as stem cell niches within the isthmus region.

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“…Broad manipulation of wingless (Wnt) signalling throughout the murine PSU reveals that low levels of Wnt promote sebaceous differentiation (Gat et al ., ; Merrill et al ., ; Niemann et al ., , ; Collins & Watt, ; Petersson et al ., ; Kakanj et al ., ; Lien et al ., ), while high levels of Wnt signalling result in SG loss and ectopic HF formation (Lo Celso, Prowse & Watt, ; Kretzschmar et al ., ). Conversely, hedgehog signalling may act to promote sebocyte differentiation (Allen et al ., ; Oro & Higgins, ; Gu & Coulombe, ).…”

Section: Introduction To Sebaceous Gland Biologymentioning

confidence: 99%

Neuroendocrinology and neurobiology of sebaceous glands

et al. 2020

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The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro-regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α-melanocyte-stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro-autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin-mediated or facial paresis-associated reduction of human sebum secretion suggests that cutaneous nerve-derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin.

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Hedgehog Signaling, Keratin 6 Induction, and Sebaceous Gland Morphogenesis

Cited by 28 publications

References 81 publications

Normal Fur Development and Sebum Production Depends on Fatty Acid 2-Hydroxylase Expression in Sebaceous Glands

Normal Fur Development and Sebum Production Depends on Fatty Acid 2-Hydroxylase Expression in Sebaceous Glands

TCF/Lef1 activity controls establishment of diverse stem and progenitor cell compartments in mouse epidermis

Neuroendocrinology and neurobiology of sebaceous glands

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