Interactions between Shh, Sostdc1 and Wnt signaling and a new feedback loop for spatial patterning of the teeth

Cho, Sung Won; Kwak, Sungwook; Woolley, Thomas E.; Lee, Min Jung; Kim, Eun Jung; Baker, Ruth E.; Kim, Hee Jin; Shin, Jeon Soo; Tickle, Cheryll; Maini, Philip K.; Jung, Han Sung

doi:10.1242/dev.056051

Cited by 113 publications

(157 citation statements)

References 40 publications

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“…Hair, feathers, glands, teeth, taste buds, and intestinal crypt villi are similarly induced under the direction of epithelial and mesenchymal interactions. Similar reaction-diffusion models have been proposed to control the size and spacing of manifold placode-derived organs (3), such as hair (4), feathers (5), and teeth (6). Activators and inhibitors in the bone morphogenetic protein (BMP), fibroblast growth factor (FGF), Hedgehog (Hh), and Wingless (Wnt) pathways execute the pattern.…”

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confidence: 99%

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Coevolutionary patterning of teeth and taste buds

Bloomquist

Parnell

Phillips

et al. 2015

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

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Teeth and taste buds are iteratively patterned structures that line the oro-pharynx of vertebrates. Biologists do not fully understand how teeth and taste buds develop from undifferentiated epithelium or how variation in organ density is regulated. These organs are typically studied independently because of their separate anatomical location in mammals: teeth on the jaw margin and taste buds on the tongue. However, in many aquatic animals like bony fishes, teeth and taste buds are colocalized one next to the other. Using genetic mapping in cichlid fishes, we identified shared loci controlling a positive correlation between tooth and taste bud densities. Genome intervals contained candidate genes expressed in tooth and taste bud fields. sfrp5 and bmper, notable for roles in Wingless (Wnt) and bone morphogenetic protein (BMP) signaling, were differentially expressed across cichlid species with divergent tooth and taste bud density, and were expressed in the development of both organs in mice. Synexpression analysis and chemical manipulation of Wnt, BMP, and Hedgehog (Hh) pathways suggest that a common cichlid oral lamina is competent to form teeth or taste buds. Wnt signaling couples tooth and taste bud density and BMP and Hh mediate distinct organ identity. Synthesizing data from fish and mouse, we suggest that the Wnt-BMP-Hh regulatory hierarchy that configures teeth and taste buds on mammalian jaws and tongues may be an evolutionary remnant inherited from ancestors wherein these organs were copatterned from common epithelium.quantitative trait loci | tooth/taste bud development | placode patterning | bipotency | plasticity

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confidence: 99%

“…Feedback loops have been independently identified wherein Wnt drives the initiation of dental (8) or taste (9) placodes. Wnt/β-catenin acts upstream of BMP and Hh signaling (10,11), which in turn may regulate Wnt and organ identity (5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Coevolutionary patterning of teeth and taste buds

Bloomquist

Parnell

Phillips

et al. 2015

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

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“…These genes are required at different stages in sweat gland development. 30,31 The downstream gene Cyclin D1 is a b-catenin target gene whose expression is upregulated during the process of aged epidermal cell dedifferentiation. 32 Therefore, we sought to identify whether key developmental sweat gland factors could directly reprogram fibroblasts into sweat gland-like cells in vitro, with the assumption that the in vivo environment may ultimately permit further reprogramming.…”

Section: Discussionmentioning

confidence: 99%

Direct reprogramming of human fibroblasts into sweat gland-like cells

Zhao

et al. 2015

Cell Cycle

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These authors contributed equally to this work.Keywords: fibroblast, Lef-1, NF-kB, reprogramming, regeneration, sweat glands Abbreviations: CEA, carcinoembryonic antigen; CK7, cytokeratin 7; CK14, cytokeratin 14; CK19, cytokeratin 19; DMEM, Dulbecco's modified Eagle's medium; FBS, fetal bovine serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Lef-1, lymphoid enhancer-binding factor 1; min, minutes; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; Shh, sonic hedgehogThe skin of patients with an extensive deep burn injury is repaired by a process that leaves a hypertrophic scar without sweat glands and therefore loses the function of perspiration. The aim of this study was to identify whether the key factors related to sweat gland development could directly reprogram fibroblasts into sweat gland-like cells. After introducing the NF-kB and Lef-1 genes into fibroblasts, we found that stably transfected fibroblasts expressed specific markers of sweat glands, including CEA, CK7, CK14 and CK19, both at the protein and mRNA levels. The immunofluorescence staining also showed positive expression of CEA, CK7, CK14 and CK19 in induced fibroblasts, but there were no positive cells in the control groups. The expression of Shh and Cyclin D1, downstream genes of NF-kB and Lef-1, were also significantly increased during regeneration. The induced fibroblasts were implanted into an animal model. Twenty days later, iodine-starch perspiration tests showed that 7 out of the 10 cell-treated paws were positive for perspiration, with a distinctive black point-like area appearing in the center of the paw. Contralateral paws tested negative. Histological examination of skin biopsies from experimental and control paws revealed that sweat glands were fully reconstructed in the test paws, with integral, secretory and ductal portions, but were not present in the control paws. This is the first report of successful reprogramming of fibroblasts into sweat gland-like cells, which will provide a new cell source for sweat gland regeneration in patients with extensive deep burns.

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“…3,4 This advance has led to the formulation of additional differential equations with nonhomogeneous initial conditions to generate the asymmetric order of multiple-structure formation in various complex patterns such as teeth, scales, feathers, hair, and other skin appendages during embryogenesis. [5][6][7][8][9][10][11] Such complexities are likely predefined genetically and allocated appropriately on the segmented skin of each animal species.…”

Section: 2mentioning

confidence: 99%

Role of the boundary in feather bud formation on one-dimensional bioengineered skin

Ishida

Mitsui

2018

APL Bioengineering

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The role of a boundary in pattern formation from a homogenous state in Turing's reaction–diffusion equations is important, particularly when the domain size is comparable to the pattern scale. Such experimental conditions may be achieved for in vitro regeneration of ectodermal appendages such as feathers, via reconstruction of embryonic single cells. This procedure can eliminate a predefined genetic map, such as the midline of chick feather bud formation, leaving uniformly distributed identical cells as a bioengineered skin. Here, the self-organizing nature of multiple feather bud formation was examined in bioengineered 1D-skin samples. Primal formation of feather buds occurred at a fixed length from the skin edge. This formation was numerically recapitulated by a standard two-component reaction-diffusion model, suggesting that the boundary effect caused this observation. The proper boundary conditions were nonstandard, either mixed Dirichlet–Neumann or partial-flux. In addition, the model implies imperfect or hindered bud formation as well as nearly equal distances between buds. In contrast, experimental observations indicated that the skin curvature, which was not included in our model, also strongly affected bud formation. Thus, bioengineered skin may provide an ideal template for modeling a self-organized process from a homogenous state. This study will examine the possible diffusion activities of activator or inhibitor molecular candidates and mechanical activities during cell aggregation, which will advance our understanding of skin appendage regeneration from pluripotent or embryonic stem cells.

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Interactions between Shh, Sostdc1 and Wnt signaling and a new feedback loop for spatial patterning of the teeth

Cited by 113 publications

References 40 publications

Coevolutionary patterning of teeth and taste buds

Coevolutionary patterning of teeth and taste buds

Direct reprogramming of human fibroblasts into sweat gland-like cells

Role of the boundary in feather bud formation on one-dimensional bioengineered skin

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