Sonic hedgehog signaling is essential for hair development

St-Jacques, Benoit; Dassule, Hélène R.; Karavanova, Irina; Botchkarev, Vladimir A.; Li, J.; Danielian, Paul S.; McMahon, Jill A.; Lewis, Paula; Paus, Ralf; McMahon, Andrew P.

doi:10.1016/s0960-9822(98)70443-9

Cited by 694 publications

(582 citation statements)

References 37 publications

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“…In E17.5 wild-type epidermis few Ptch1 (Figure 1b In order to define the spatio-temporal distribution of Hh signalling activity during HF development we quantitated the Ptch1 and Gli1 transcript density along the proximal-distal length of HFs at different stages of the HF cycle. Previous studies have shown that Hh signalling is dispensable for HF initiation and hair germ development (stage 2) (Chiang et al, 1999;St-Jacques et al, 1998). Consistent with these findings, we observed low levels (90% (Figure 3a, c, e and g) concurrently exhibit decreased e-cadherin (Figure 3b and f), p120-catenin (Figure 3d and h) and ZO-1 (data not shown) expression.…”

Section: Resultssupporting

confidence: 92%

Patched Receptors Sense, Interpret, and Establish an Epidermal Hedgehog Signaling Gradient

Adolphe

Junker

Lyubimova

et al. 2017

Journal of Investigative Dermatology

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By employing the sensitivity of single molecule fluorescent in situ hybridisation (smFISH) we have precisely quantified the levels and defined the temporal and spatial distribution of Hedgehog signalling activity during embryonic skin development, and uncovered that there is a Hedgehog signalling gradient along the proximal-distal axis of developing hair follicles. In order to explore the contribution of Hedgehog receptors Ptch1 and Ptch2 in establishing the epidermal signalling gradient, we quantitated the level of pathway activity generated in Ptch1 and Ptch1;Ptch2-deficient skin and defined the contribution of each receptor to regulation of the levels of Hedgehog signalling identified in wild-type skin. Moreover, we show that both the cellular phenotype and level of pathway activity featured in Ptch1;Ptch2-deficient cells faithfully recapitulates the Peak level of endogenous Hedgehog signalling detected at the base of developing follicles, where the concentration of endogenous Shh is predicted to be highest.Taken together, these data demonstrate that both Ptch1 and Ptch2 play a crucial role in sensing the concentration of Hedgehog ligand and regulating the appropriate dose-dependent response.

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Section: Resultssupporting

confidence: 92%

Patched Receptors Sense, Interpret, and Establish an Epidermal Hedgehog Signaling Gradient

Adolphe

Junker

Lyubimova

et al. 2017

Journal of Investigative Dermatology

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“…Moreover, mitotic cells, as detected via short term BrdU incorporation are mainly in the Ptch1 expressing region, raising the likelihood that Ptch1 expressing cells comprise the transit amplifying population, and possibly the taste bud stem cells [33]. In both fungiform and circumvallate papillae, BMP4-ß-gal-expressing cells may lie adjacent to the Ptch1 expressing cells, or may express Ptc1 suggesting the possibility that BMP4 and SHH may coordinate taste cell turnover, as has been demonstrated for regeneration of a number of other epithelial appendages, including hair follicles [76,77]. …”

Section: Discussionmentioning

confidence: 99%

Differential expression of a BMP4 reporter allele in anterior fungiform versus posterior circumvallate taste buds of mice

Nguyen

Barlow

2010

BMC Neurosci

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BackgroundBone Morphogenetic Protein 4 (BMP4) is a diffusible factor which regulates embryonic taste organ development. However, the role of BMP4 in taste buds of adult mice is unknown. We utilized transgenic mice with LacZ under the control of the BMP4 promoter to reveal the expression of BMP4 in the tongues of adult mice. Further we evaluate the pattern of BMP4 expression with that of markers of specific taste bud cell types and cell proliferation to define and compare the cell populations expressing BMP4 in anterior (fungiform papillae) and posterior (circumvallate papilla) tongue.ResultsBMP4 is expressed in adult fungiform and circumvallate papillae, i.e., lingual structures composed of non-taste epithelium and taste buds. Unexpectedly, we find both differences and similarities with respect to expression of BMP4-driven ß-galactosidase. In circumvallate papillae, many fusiform cells within taste buds are BMP4-ß-gal positive. Further, a low percentage of BMP4-expressing cells within circumvallate taste buds is immunopositive for markers of each of the three differentiated taste cell types (I, II and III). BMP4-positive intragemmal cells also expressed a putative marker of immature taste cells, Sox2, and consistent with this finding, intragemmal cells expressed BMP4-ß-gal within 24 hours after their final mitosis, as determined by BrdU birthdating. By contrast, in fungiform papillae, BMP4-ß-gal positive cells are never encountered within taste buds. However, in both circumvallate and fungiform papillae, BMP4-ß-gal expressing cells are located in the perigemmal region, comprising basal and edge epithelial cells adjacent to taste buds proper. This region houses the proliferative cell population that gives rise to adult taste cells. However, perigemmal BMP4-ß-gal cells appear mitotically silent in both fungiform and circumvallate taste papillae, as we do not find evidence of their active proliferation using cell cycle immunomarkers and BrdU birthdating.ConclusionOur data suggest that intragemmal BMP4-ß-gal cells in circumvallate papillae are immature taste cells which eventually differentiate into each of the 3 taste cell types, whereas perigemmal BMP4-ß-gal cells in both circumvallate and fungiform papillae may be slow cycling stem cells, or belong to the stem cell niche to regulate taste cell renewal from the proliferative cell population.

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“…The hedgehog signalling pathway is one of the most fundamental signal transduction pathways in embryonic development, being responsible for patterning the developing neural tube, axial skeleton, limbs, lungs, skin, hair and teeth (Bellusci et al, 1997;Hardcastle et al, 1998;Marigo and Tabin, 1996;Riddle et al, 1993;St-Jacques et al, 1998). Much of what is known of the function of this pathway has been derived from studies in Drosophila, and many of the key elements have been conserved from¯ies through to humans Hahn et al, 1996a).…”

Section: Abstract: Patched; Hedgehog; Basal Cell Carcinomamentioning

confidence: 99%

“…In vitro studies suggest that each of these proteins can act through the same signal transduction pathway, and that the di erent hedgehog genes regulate patterning of di erent organ systems by virtue of their unique expression pattern (Echelard et al, 1993;Marigo et al, 1996;Stone et al, 1996). The most extensively studied of the vertebrate hedgehog genes is Shh which is expressed widely throughout the developing CNS, limb, lung, gut, teeth and hair-follicle (Bellusci et al, 1997;Hardcastle et al, 1998;Litingtung et al, 1998;Marigo and Tabin, 1996;Riddle et al, 1993;St-Jacques et al, 1998). Dhh and Ihh are primarily involved in development of the germline and skeletal system respectively (Bitgood et al, 1996;Vortkamp et al, 1996).…”

Section: Hedgehog Signalling Pathwaymentioning

confidence: 99%

The hedgehog signalling pathway in tumorigenesis and development

1999

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Sonic hedgehog signaling is essential for hair development

Abstract: Shh signaling is not required for initiating hair follicle development. Shh signaling is essential, however, for controlling ingrowth and morphogenesis of the hair follicle.

Cited by 694 publications

References 37 publications

Patched Receptors Sense, Interpret, and Establish an Epidermal Hedgehog Signaling Gradient

Patched Receptors Sense, Interpret, and Establish an Epidermal Hedgehog Signaling Gradient

Differential expression of a BMP4 reporter allele in anterior fungiform versus posterior circumvallate taste buds of mice

The hedgehog signalling pathway in tumorigenesis and development

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