Skin Appendage Formation Research Articles

Reinforcing decellularized small intestine submucosa with cellulose acetate nanofibrous and silver nanoparticles as a scaffold for wound healing applications.

The formation of chronicwounds accounts for considerable costs in health care systems. Despite theseveral benefits of decellularized small intestinal submucosa (SIS) as anappropriate scaffold for different tissue regeneration, it has shortcomings such as lack of antibacterial features and inappropriate mechanical properties for skin tissue regeneration. We aimed to examine the efficacy and safety of decellularized SIS scaffold enhanced with cellulose acetate (CA) and silver (Ag) nanoparticles (NPs) for healing full-thickness wounds. The scaffolds wereprepared by decellularizing bovine SIS and electrospinning CA/Ag nanoparticles and characterized using a transmission electron microscope (TEM), scanning electronmicroscope (SEM), tensile testing, and X-ray diffraction. In vivo evaluations were performed using full-thickness excisions covered with sterile gauze as the control group, SIS, SIS/CA, and SIS/CA/Ag scaffolds on the dorsum of twenty male Wistar rats divided into four groups randomly with 21-days follow-up. All in vivo specimens underwent Masson's trichrome (MT) staining for evaluation of collagen deposition, transforming growth factor-β (TGF-β) immunohistochemistry (IHC), and Haematoxylin Eosin (H&E) staining. The IHC and MT data were analyzed with the ImageJ tool by measuring the stained area. The TEM results revealedthat Ag nanoparticles are successfully incorporated into CA nanofibers. Assessment of scaffoldshydrophilicity demonstrated that the contact angle of SIS/CA/Ag scaffold was the lowest. The in vivoresults indicated that the SIS/CA/Ag scaffold had the most significant wound closure. H&E staining of the invivo specimens showed the formation of epidermal layers in the SIS/CA/Ag group on day 21. The percentage of the stained area of MT and TGF-β IHC staining's was highest in the SIS/CA/Ag group. The decellularizedSIS/CA/Ag scaffolds provided the most significant wound closure compared toother groups and caused the formation of epidermal layers and skin appendages. Additionally, the collagen deposition and expression of TGF-β increased significantly in SIS/CA/Ag group.

Composite Aerogel Scaffolds Containing Flexible Silica Nanofiber and Tricalcium Phosphate Enable Skin Regeneration.

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.

EDA ligand triggers plasma membrane trafficking of its receptor EDAR via PKA activation and SNAP23-containing complexes

BackgroundEctodysplasin-A (EDA), a skin-specific TNF ligand, interacts with its membrane receptor EDAR to trigger EDA signaling in skin appendage formation. Gene mutations in EDA signaling cause Anhidrotic/Hypohidrotic Ectodermal Dysplasia (A/HED), which affects the formation of skin appendages including hair, teeth, and several exocrine glands.ResultsWe report that EDA triggers the translocation of its receptor EDAR from a cytosolic compartment into the plasma membrane. We use protein affinity purification to show that upon EDA stimulation EDAR associates with SNAP23-STX6-VAMP1/2/3 vesicle trafficking complexes. We find that EDA-dependent PKA activation is critical for the association. Notably, either of two HED-linked EDAR mutations, T346M and R420W, prevents EDA-induced EDAR translocation; and both EDA-induced PKA activation and SNAP23 are required for Meibomian gland (MG) growth in a skin appendage model.ConclusionsOverall, in a novel regulatory mechanism, EDA increases plasma membrane translocation of its own receptor EDAR, augmenting EDA-EDAR signaling in skin appendage formation. Our findings also provide PKA and SNAP23 as potential targets for the intervention of HED.

Systemic Prenatal Stress Exposure through Corticosterone Application Adversely Affects Avian Embryonic Skin Development.

Prenatal stress exposure is considered a risk factor for developmental deficits and postnatal behavioral disorders. While the effect of glucocorticoid-associated prenatal stress exposure has been comprehensively studied in many organ systems, there is a lack of in-depth embryological investigations regarding the effects of stress on the integumentary system. To approach this, we employed the avian embryo as a model organism and investigated the effects of systemic pathologically-elevated glucocorticoid exposure on the development of the integumentary system. After standardized corticosterone injections on embryonic day 6, we compared the stress-exposed embryos with a control cohort, using histological and immunohistochemical analyses as well as in situ hybridization. The overarching developmental deficits observed in the stress-exposed embryos were reflected through downregulation of both vimentin as well as fibronectin. In addition, a deficient composition in the different skin layers became apparent, which could be linked to a reduced expression of Dermo-1 along with significantly reduced proliferation rates. An impairment of skin appendage formation could be demonstrated by diminished expression of Sonic hedgehog. These results contribute to a more profound understanding of prenatal stress causing severe deficits in the integumentary system of developing organisms.

Bioinspired Strategies for Wound Regeneration.

Regeneration allows animals to replace and restore injured tissues. Animal phyla have evolved different regenerative strategies to increase survival advantages. In contrast to the earlier principle that regeneration recapitulates development, recent studies indicate that wound healing in adult mammals is modified by the inflammatory response to injury, and biochemical signaling from immune and other cellular systems may modulate wound reparative responses to achieve successful tissue regeneration. Here we briefly survey different regenerative strategies used by animals across different phyla. We next focus on skin regeneration using the mouse wound-induced hair neogenesis model as an example to show the circumstances required to rebuild a new, morphogenetically competent field in the adult mammalian skin. Parallel investigations in African spiny mice (Acomys sp.) have further shown that skin rigidity can also modulate wound bed properties to facilitate de novo formation of skin appendages. These regenerating, periodically arranged hair primordia emerge using Turing activator/inhibitor principles with activities derived from sources that differ from those used in embryonic development, including the mechanical environment. Thus, a novel combination of biochemical, immunological, and mechanical signaling strategies can work together to achieve successful cutaneous regeneration in adult animals, potentially inspiring novel therapeutic strategies.

Ectodysplasin A (EDA) Signaling: From Skin Appendage to Multiple Diseases.

Ectodysplasin A (EDA) signaling is initially identified as morphogenic signaling regulating the formation of skin appendages including teeth, hair follicles, exocrine glands in mammals, feathers in birds and scales in fish. Gene mutation in EDA signaling causes hypohidrotic ectodermal dysplasia (HED), a congenital hereditary disease with malformation of skin appendages. Interestingly, emerging evidence suggests that EDA and its receptors can modulate the proliferation, apoptosis, differentiation and migration of cancer cells, and thus may regulate tumorigenesis and cancer progression. More recently, as a newly discovered hepatocyte factor, EDA pathway has been demonstrated to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and type II diabetes by regulating glucose and lipid metabolism. In this review, we summarize the function of EDA signaling from skin appendage development to multiple other diseases, and discuss the clinical application of recombinant EDA protein as well as other potential targets for disease intervention.

Platelet rich fibrin containing nanofibrous dressing for wound healing application: Fabrication, characterization and biological evaluations

Recently, nanofibrous structures have shown great potential for a wide range of medical applications. The aim of the current study was to evaluate the wound healing process using Polycaprolactone/Keratin/Platelet-rich fibrin (PCL/Kr/PRF) fibrous scaffold fabricated through electrospinning process. A range of techniques were utilized to fully characterize the chemical, physical and biological properties of the resultant structure. Results revealed that by the addition of only 0.5%w/v PRF to PCL/Kr (PCL/Kr/0.5PRF) sample, the fibers diameter decreased from 193.93 ± 64.80 nm to 65.98 ± 14.03 nm, and the stress at break demonstrated a 18.27% increase in comparison to the PCL sample (from 2.90 ± 0.80 MPa to 3.43 ± 0.90 MPa). The PCL/Kr/0.5PRF scaffold showed more antibacterial activity against gram-positive and gram-negative bacteria than PCL/Kr sample. Based on enzyme-linked immunosorbent assays, the PCL/Kr/0.5PRF sample revealed an independent release of VEGF and PDGF for 7 days. Cell viability studies demonstrated non-cytotoxic nature of PRF-containing dressings. Also, chorioallantoic membrane (CAM) assay was performed to evaluate the angiogenic potential of the wound dressings. The in vivo assessments also showed that PCL/Kr/0.5PRF accelerated the wound healing process in terms of collagen deposition and the formation of skin appendages which was comparable to the normal skin. Overall, the data presented in this study greatly suggest that the PCL/Kr/0.5PRF wound dressing could be a suitable candidate for wound healing and skin regeneration.

Bioinspired, injectable, tissue-adhesive and antibacterial hydrogel for multiple tissue regeneration by minimally invasive therapy

Hemorrhage and wound infection after soft tissue trauma are the main factors causing casualties in surgical procedures and disasters. Currently available tissue adhesives for hemorrhage and wound infection treatment remain unsatisfactory due to the lack of ideal adhesive hydrogels that can integrate injectability, tunable mechanical strength, matching irregular defect and antibacterial property into one system. Here, inspired by the mussel adhesive protein and the natural extracellular matrix (ECM) composition, we engineered a gelatin-based adhesive hydrogel (Dopamine modified methacrylate gelatin, GMDA) with strong tissue adhesiveness and antibacterial property. This bioinspired injectable hydrogel demonstrated tunable mechanical properties and optimal elasticity due to the double-crosslinked network formed through the horseradish peroxidase (HRP) / hydrogen peroxide (H2O2) and ultraviolet (UV) light crosslinking. In addition, these adhesive hydrogels could withstand up to 250 mmHg blood pressure (significantly higher than normal blood pressure, systolic BP 60–160 mmHg) and showed superior hemostasis capability of uncontrolled bleeding in vivo. Most importantly, the hydrogel exhibited significant antibacterial property because of the released residual H2O2 after hydrogel formation. Further in vivo studies demonstrated that the hydrogel loaded with epidermal growth factor (EGF) could promote efficient skin regeneration with the formation of skin appendages. These findings shed new light on developing a multifunctional bioinspired adhesive hydrogel that could serve as a promising biomaterial for hemostasis and wound infection treatment and other minimally invasive use of biomedical applications.

Development of Poloxamer Hydrogels Containing Antibacterial Guanidine-Based Polymers for Healing of Full-Thickness Skin Wound.

A series of hydrogels containing guanidine-based polymers using a poloxamer as the matrix were prepared to provide novel wound dressings with antibacterial and repairing-promotion properties for skin wounds. Herein, we developed a series of antibacterial hydrogels, the cationic guanidine-based polymer polyhexamethylene guanidine hydrochloride (PHMG) with poloxamer aqueous solution (12%, w/w) simplified as PHMGP, chitosan (CS)-cross-linked PHMG (referred to as PHMC) with poloxamer aqueous solution simplified as PHMCP, and hyaluronic acid (HA)-modified PHMG (referred to as PHMH) with poloxamer aqueous solution simplified as PHMHP, for enhancing full-thickness skin wound healing. The characterizations, antimicrobial activity, cytotoxicity, and in vivo full-thickness wound-healing capability of these hydrogels were analyzed and evaluated. The results show that though PHMGP possesses great bactericide properties, its cytotoxicity is too strong to support skin regeneration. However, after modified with CS or HA, PHMCP and PHMHP showed good biocompatibility and antimicrobial properties against Gram-positive and Gram-negative bacteria that are commonly present in injured skin. Both PHMCP and PHMHP hydrogels exhibited upgraded wound-healing efficiency in full-thickness skin defects, characterized by a shorter wound closure time, faster re-regeneration, and the earlier formation of skin appendages, compared with those of control or pure poloxamer treatments. Their biological mechanism was detected. Both PHMCP and PHMHP can regulate the related biofactors during the skin repair process such as interleukin-1β (IL-1β), interleukin-6 (IL-6), transforming growth factor beta-1(TGF-β1), alpha-smooth muscle actin (α-SMA), and vascular endothelial growth factor, to promote wound healing with less serious scarring. In short, hydrogels with excellent capabilities to inhibit microorganism infection and promote wound healing were developed, which will shed light on designing and producing wound dressings with promising applications in future.

Zebrafish twist2/dermo1 regulates scale shape and scale organization during skin development and regeneration.

Scales are skin appendages in fishes that evolutionarily predate feathers in birds and hair in mammals. Zebrafish scales are dermal in origin and develop during metamorphosis. Understanding regulation of scale development in zebrafish offers an exciting possibility of unraveling how the mechanisms of skin appendage formation evolved in lower vertebrates and whether these mechanisms remained conserved in birds and mammals. Here we have investigated the expression and function of twist 2/dermo1 gene - known for its function in feather and hair formation - in scale development and regeneration. We show that of the four zebrafish twist paralogues, twist2/dermo1 and twist3 are expressed in the scale forming cells during scale development. Their expression is also upregulated during scale regeneration. Our knockout analysis reveals that twist2/dermo1 gene functions in the maintenance of the scale shape and organization during development as well as regeneration. We further show that the expression of twist2/dermo1 and twist3 is regulated by Wnt signaling. Our results demonstrate that the function of twist2/dermo1 in skin appendage formation, presumably under regulation of Wnt signaling, originated during evolution of basal vertebrates.

A bilayered skin substitute developed using an eggshell membrane crosslinked gelatin-chitosan cryogel.

Commercially available allografts and xenografts pose problems such as high cost, risk of infection transmission and immune rejection of grafts. Thus, bioengineered skin substitutes fabricated from natural biomaterials or synthetic polymers are currently the focus of skin tissue engineering. In this study, eggshell membrane (ESM) powder was used to crosslink a gelatin-chitosan cryogel thereby replacing glutaraldehyde, a known cytotoxic chemical crosslinker. The resultant ESM-crosslinked macroporous cryogel with a pore size ranging between 10 and 350 μm has improved flexibility, biodegradability and biocompatibility compared to a glutaraldehyde-crosslinked cryogel. For healing of large and deep wounds, bilayered scaffolds which exhibit key aspects of skin physiology are being explored. Hence, we fabricated a bilayered substitute by coupling the ESM-crosslinked cryogel (dermal equivalent) to a non-porous, physically-crosslinked gelatin-chitosan film (epidermal equivalent). The epidermal layer provides the requisite barrier properties while the dermal layer facilitates cell attachment and migration for optimal wound healing. Further, chitosan confers antibacterial properties to the cryogel with almost 50% reduction in bacterial viability. Animal studies confirm that the developed bilayered skin substitute is non-allergic, aids wound healing by improving re-epithelialization within 14 days and supports the formation of skin appendages. This system presents a new and alternative treatment option for burn and chronic wounds.

Methods for the Administration of EDAR Pathway Modulators in Mice.

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia, a congenital condition characterized by the absence or abnormal formation of sweat glands, teeth, and several skin appendages. Stimulation of the EDA receptor (EDAR) with agonists in the form of recombinant EDA or anti-EDAR antibodies can compensate for the absence of Eda in a mouse model of Eda deficiency, provided that agonists are administered in a timely manner during fetal development. Here we provide detailed protocols for the administration of EDAR agonists or antagonists, or other proteins, by the intravenous, intraperitoneal, and intra-amniotic routes as well as protocols to collect blood, to visualize sweat gland function, and to prepare skulls in mice.

Zinc sulfide nanoparticles improve skin regeneration

Wound healing has been intensely studied to expedite recovery times and reduce scarring. However, current technologies fail to achieve regenerative capabilities, leaving wounds with scarring and lack of skin accessories. The recent emergence of nanotechnology has provided a new clinical modality of zinc nanoparticles in wound care. This present study investigated Zinc Sulfide nanoparticles (ZnS-NP) on wound healing in vitro with 2D and 3D models and in vivo with rat full-thickness wound model. ZnS-NP inhibited fetal bovine serum-stimulated rat skin fibroblast cell proliferation, altered cytoskeletal organization, and reduced collagen synthesis as well as contractile activity. ZnS-NP regulated redox homeostatsis and promoted fibroblast viability in 3D hypoxia conditions. In the rat full-thickness wound model, ZnS-NP reduced wound contraction, enhanced re-epithelization, and promoted skin appendage formation. The biological activities of ZnS-NPs determined in our current study may suggest promising practical applications for topical or systemic treatment for wound repair.

Electrospun chitosan/PVA/bioglass Nanofibrous membrane with spatially designed structure for accelerating chronic wound healing.

Cutaneous wounds, especially chronic wounds, remain clinical challenges, and this is partially due to the complex healing process composed of four overlapping but distinct stages including hemostasis, inflammation, proliferation and remodeling. Therefore, wound dressings with spatially designed structures which can temporally regulate certain bioactive components to function at specific healing stages might be able to accelerate the healing process. In this study, nanobioglass incorporated chitosan-PVA (polyvinyl alcohol) trilayer nanofibrous membrane (nBG-TFM) was fabricated via sequential electrospinning. This membrane exhibited excellent biocompatibility, antibacterial activity and regeneration promotion effect. Furthermore, spatially designed structure optimized functions of each component and provided more suitable microenvironment as compared with uniform membrane. Rat full-thickness skin defects model and mice diabetic chronic wound model showed that nBG-TFM could achieve significantly accelerated and enhanced healing, in terms of complete re-epithelialization, improved collagen alignment and formation of skin appendages. It was revealed that nBG-TFM functioned through upregulating growth factors including VEGF and TGF-β. Meanwhile inflammatory cytokines such as TNF-α and IL-1β were downregulated. The technology presented in this study shed new light on designing functional wound dressings which can promote healing of chronic wounds.

Evolution and Developmental Diversity of Skin Spines in Pufferfishes.

SummaryTeleost fishes develop remarkable varieties of skin ornaments. The developmental basis of these structures is poorly understood. The order Tetraodontiformes includes diverse fishes such as the ocean sunfishes, triggerfishes, and pufferfishes, which exhibit a vast assortment of scale derivatives. Pufferfishes possess some of the most extreme scale derivatives, dermal spines, erected during their characteristic puffing behavior. We demonstrate that pufferfish scale-less spines develop through conserved gene interactions that underlie general vertebrate skin appendage formation, including feathers and hair. Spine development retains conservation of the EDA (ectodysplasin) signaling pathway, important for the development of diverse vertebrate skin appendages, including these modified scale-less spines of pufferfish. Further modification of genetic signaling from both CRISPR-Cas9 and small molecule inhibition leads to loss or reduction of spine coverage, providing a mechanism for skin appendage diversification observed throughout the pufferfishes. Pufferfish spines have evolved broad variations in body coverage, enabling adaptation to diverse ecological niches.

From Scale to Spine: Evolution and Developmental Diversity of Skin Spines in Pufferfishes

Teleost fishes develop a remarkable variety of skin ornaments. However, the developmental basis of these structures is poorly understood. The teleost order Tetraodontiformes includes diverse fishes such as the ocean sunfishes, triggerfishes and pufferfishes, which exhibit a vast assortment of scale derivatives. Pufferfishes and porcupine fishes possess some of the most extreme scale derivatives, dermal spines, which are erected during their characteristic puffing behavior. Here, we focus on pufferfishes and demonstrate that the spines develop through conserved gene interactions that underlie skin appendage formation throughout other vertebrates, including avian feathers and mammalian hair. Pufferfish spine development retains the conserved role of the EDA (ectodysplasin) signaling pathway, suggesting that EDA is an important molecule/pathway for the development of diverse vertebrate skin appendages, including these modified scale-less spines of the pufferfish lineage. Further modification of genetic signaling from both CRISPR-Cas9 and small molecule inhibition can lead to both loss or reduction of spine coverage in pufferfish, providing a mechanism for skin appendage diversification observed in the extant clade of pufferfishes (Tetraodontidae). Dermal spines are unique scale-derivatives that evolved through conserved gene network modification. In pufferfish they exhibit broad variation in coverage, enabling adaptation to diverse ecological niches.

Changes in Placental Morphology and their Association with Embryonic Skin Development

Abstract Histogenesis and organogenesis in mammals normally transpires in a hypoxic environment. Oxygen diffusing capacity is dependent on diffusion distance, which may vary with the thickness of placental barrier and with the level of tissue vascularity. Since the epidermis is avascular, its development fully depends on dermal blood vessels. Despite the large number of studies focusing on uteroplacental circulation and embryogenesis, it is clear that the current knowledge of how placental changes in pregnancy contribute to skin development is incomplete. The aim of this study was to evaluate the association between structural changes in the placental barrier and development of the integumentary system, with special reference to dermal angiogenesis. The study included specimens of six embryos and ten foetuses from 5 to 24 developmental weeks, and 21 specimens of placental tissue 6–40 weeks gestational age. The panel of antibodies used was S- 100, SMA, CD31, CD34, AE1/AE3 (PCKT), CKRT7, CD 56 and hCG. During the first trimester, maternal blood flow to the placenta appears to be initially restricted by trophoblast plugs. Natural killer cells appear in great abundance in subendothelium of decidual blood vessels, potentially stimulating extensive angiogenesis. By the end of the first trimester, new capillary beds organise to supply the developing epidermal derivatives. During the second trimester, the placental barrier becomes progressively thinner, and uteroplacental circulation is established due to dissolution of endovascular trophoblast plugs. Progression of the formation of skin appendages, hypodermal adipose tissue, demarcation of papillary and reticular dermis, and keratinisation of interfollicular epidermis in the second trimester strongly accompanies the dermal angiogenesis and placental maturation.

A dual deformable liposomal ointment functionalized with retinoic acid and epidermal growth factor for enhanced burn wound healing therapy.

An ointment containing retinoic acid deformable liposomes (TRA DLs) and epidermal growth factor cationic deformable liposomes (EGF CDLs) was prepared for the treatment of deep partial-thickness burns. The characterization tests confirmed both liposomes featured small particle sizes, high drug entrapment efficiencies and sustained drug release behavior. Compared with the free drug, TRA DLs and EGF CDLs exhibited superior skin permeation and remarkably increased drug deposition by 2.9 and 18.8 folds, respectively. Results on HaCaT cells indicated the combined application of two liposomes exerted a synergistic effect and prominently promoted cell proliferation and migration. Application of the dual liposomal ointment on a deep partial-thickness burn model stimulated wound closure (p < 0.001), promoted skin appendage formation and increased collagen production, thus improving healing quality. Finally, it was demonstrated that TRA significantly up-regulated the expression of EGFR and HB-EGF to enhance the therapeutic effect of EGF. Therefore, the dual liposomal ointment is a promising topical therapeutic for burn treatment.

Fishing for ancestry.

The same genes and signalling pathways control the formation of skin appendages in both fish and land animals.

Eda-activated RelB recruits an SWI/SNF (BAF) chromatin-remodeling complex and initiates gene transcription in skin appendage formation

Ectodysplasin A (Eda) signaling activates NF-κB during skin appendage formation, but how Eda controls specific gene transcription remains unclear. Here, we find that Eda triggers the formation of an NF-κB-associated SWI/SNF (BAF) complex in which p50/RelB recruits a linker protein, Tfg, that interacts with BAF45d in the BAF complex. We further reveal that Tfg is initially induced by Eda-mediated RelB activation and then bridges RelB and BAF for subsequent gene regulation. The BAF component BAF250a is particularly up-regulated in skin appendages, and epidermal knockout of BAF250a impairs skin appendage development, resulting in phenotypes similar to those of Eda-deficient mouse models. Transcription profiling identifies several target genes regulated by Eda, RelB, and BAF. Notably, RelB and the BAF complex are indispensable for transcription of Eda target genes, and both BAF complex and Eda signaling are required to open chromatin of Eda targets. Our studies thus suggest that Eda initiates a signaling cascade and recruits a BAF complex to specific gene loci to facilitate transcription during organogenesis.