Recombinant EDA or Sonic Hedgehog rescue the branching defect in Ectodysplasin A pathway mutant salivary glands in vitro

Wells, Kirsty L.; Mou, Chunyan; Headon, Denis J.; Tucker, Abigail S.

doi:10.1002/dvdy.22406

Cited by 21 publications

(25 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data combined with the fact that the expression level of Shh positively correlated with Eda signaling activity in vivo, implicates Shh as a key mediator downstream of Eda in developing salivary glands. While our manuscript was under review, Wells et al (Wells et al, 2010) reported the rescue of an Edar-deficient SMG branching defect (which was similar to that seen in Eda-null embryos) produced by recombinant Shh protein, further confirming the importance of Shh downstream of Eda/Edar.…”

Section: Discussionsupporting

confidence: 68%

“…In line with this, qRT-PCR analysis of Eda-null SMGs at later stages (E16 to newborn) indicated that both Shh and Fgf8 were downregulated (Melnick et al, 2009). Wells et al (Wells et al, 2010) reported that treatment with Fgf8 protein did not rescue the branching defect of Edar mutant SMGs, but did increase bud surface area. It is likely that many signaling molecules, acting either in the same or in parallel pathways, function as proliferative cues to promote epithelial growth and branching of SMG (Patel et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ectodysplasin and Wnt pathways are required for salivary gland branching morphogenesis

et al. 2011

View full text Add to dashboard Cite

SUMMARYThe developing submandibular salivary gland (SMG) is a well-studied model for tissue interactions and branching morphogenesis. Its development shares similar features with other ectodermal appendages such as hair and tooth. The ectodysplasin (Eda) pathway is essential for the formation and function of several ectodermal organs. Mutations in the signaling components of the Eda pathway lead to a human syndrome known as hypohidrotic ectodermal dysplasia (HED), which is characterized by missing and malformed teeth, sparse hair and reduced sweating. Individuals with HED suffer also from dry mouth because of reduced saliva flow. In order to understand the underlying mechanism, we analyzed salivary gland development in mouse models with altered Eda pathway activities. We have found that Eda regulates growth and branching of the SMG via transcription factor NFkB in the epithelium, and that the hedgehog pathway is an important mediator of Eda/NF-kB. We also sought to determine whether a similar reciprocal interplay between the Eda and Wnt/b-catenin pathways, which are known to operate in other skin appendages, functions in developing SMG. Surprisingly and unlike in developing hair follicles and teeth, canonical Wnt signaling activity did not colocalize with Edar/NF-kB in salivary gland epithelium. Instead, we observed high mesenchymal Wnt activity and show that ablation of mesenchymal Wnt signaling either in vitro or in vivo compromised branching morphogenesis. We also provide evidence suggesting that the effects of mesenchymal Wnt/b-catenin signaling are mediated, at least in part, through regulation of Eda expression.

show abstract

Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Ectodysplasin and Wnt pathways are required for salivary gland branching morphogenesis

et al. 2011

View full text Add to dashboard Cite

show abstract

“…This ex ovo rescue study [50] implicated defective FGF signalling as underlying the failure of feather development in sc/sc , though such mutant rescue data should be interpreted cautiously in the absence of genetic evidence, since it is possible that such phenotypic rescues are achieved via a pathway independent or downstream of the primary causative genetic defect. For example, it has been shown that tooth and gland defects in Eda mutant mice can be rescued with recombinant Fgf10 and Shh, as well as by recombinant Eda itself [51,52]. …”

Section: Discussionmentioning

confidence: 99%

Genome-wide SNP scan of pooled DNA reveals nonsense mutation in FGF20 in the scaleless line of featherless chickens

et al. 2012

View full text Add to dashboard Cite

BackgroundScaleless (sc/sc) chickens carry a single recessive mutation that causes a lack of almost all body feathers, as well as foot scales and spurs, due to a failure of skin patterning during embryogenesis. This spontaneous mutant line, first described in the 1950s, has been used extensively to explore the tissue interactions involved in ectodermal appendage formation in embryonic skin. Moreover, the trait is potentially useful in tropical agriculture due to the ability of featherless chickens to tolerate heat, which is at present a major constraint to efficient poultry meat production in hot climates. In the interests of enhancing our understanding of feather placode development, and to provide the poultry industry with a strategy to breed heat-tolerant meat-type chickens (broilers), we mapped and identified the sc mutation.ResultsThrough a cost-effective and labour-efficient SNP array mapping approach using DNA from sc/sc and sc/+ blood sample pools, we map the sc trait to chromosome 4 and show that a nonsense mutation in FGF20 is completely associated with the sc/sc phenotype. This mutation, common to all sc/sc individuals and absent from wild type, is predicted to lead to loss of a highly conserved region of the FGF20 protein important for FGF signalling. In situ hybridisation and quantitative RT-PCR studies reveal that FGF20 is epidermally expressed during the early stages of feather placode patterning. In addition, we describe a dCAPS genotyping assay based on the mutation, developed to facilitate discrimination between wild type and sc alleles.ConclusionsThis work represents the first loss of function genetic evidence supporting a role for FGF ligand signalling in feather development, and suggests FGF20 as a novel central player in the development of vertebrate skin appendages, including hair follicles and exocrine glands. In addition, this is to our knowledge the first report describing the use of the chicken SNP array to map genes based on genotyping of DNA samples from pooled whole blood. The identification of the sc mutation has important implications for the future breeding of this potentially useful trait for the poultry industry, and our genotyping assay can facilitate its rapid introgression into production lines.

show abstract

“…An air interface technique was used because full liquid submersion resulted in dissociation of overlying epidermis. The air interphase technique has been used successfully for other explants of tissue normally fully submerged in vivo (Wells et al, 2010; Bull et al, 2011). Others have shown that air interface can accelerate barrier development in rats (Komuves et al, 1999), however human tissue used in these studies is developmentally 8–12 weeks from this stage and it remains unknown whether air interface might have a similar effect on human scalp development.…”

Section: Methodsmentioning

confidence: 99%

CD133 Expression Correlates with Membrane Beta-Catenin and E-Cadherin Loss from Human Hair Follicle Placodes during Morphogenesis

Yang¹,

Plikus

Ito

et al. 2015

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Genetic studies suggest that the major events of human hair follicle development are similar to those in mice, but detailed analyses of this process are lacking. In mice, hair follicle placode ‘budding’ is initiated by invagination of Wnt-induced epithelium into the underlying mesenchyme. Modification of adherens junctions is clearly required for budding. Snail-mediated downregulation of adherens junction component E-cadherin is important for placode budding in mice. Beta-catenin, another adherens junction component, has been more difficult to study due to its essential functions in Wnt signaling, a prerequisite for hair follicle placode induction. Here, we show that a subset of human invaginating hair placode cells expresses the stem cell marker CD133 during early morphogenesis. CD133 associates with membrane beta-catenin in early placodes and its continued expression correlates with loss of beta-catenin and E-cadherin from the cell membrane at a time when E-cadherin transcriptional repressors Snail and Slug are not implicated. Stabilization of CD133 via anti-CD133 antibody treatment of human fetal scalp explants depresses beta-catenin and E-cadherin membrane localization. We discuss this unique correlation and suggest a hypothetical model whereby CD133 promotes morphogenesis in early hair follicle placodes through the localized removal of membrane beta-catenin proteins and subsequent adherens junction dissolution.

show abstract

Recombinant EDA or Sonic Hedgehog rescue the branching defect in Ectodysplasin A pathway mutant salivary glands in vitro

Cited by 21 publications

References 38 publications

Ectodysplasin and Wnt pathways are required for salivary gland branching morphogenesis

Ectodysplasin and Wnt pathways are required for salivary gland branching morphogenesis

Genome-wide SNP scan of pooled DNA reveals nonsense mutation in FGF20 in the scaleless line of featherless chickens

CD133 Expression Correlates with Membrane Beta-Catenin and E-Cadherin Loss from Human Hair Follicle Placodes during Morphogenesis

Contact Info

Product

Resources

About