Gap junctions in Turing-type periodic feather pattern formation.

Periodic patterning requires coordinated cell-cell interactions at the tissue level. Turing showed, using mathematical modeling, how spatial patterns could arise from the reactions of a diffusive activator-inhibitor pair in an initially homogeneous 2D field. Most activators and inhibitors studied in biological systems are proteins, and the roles of cell-cell interaction, ions, bioelectricity, etc.

Epidermal-dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures.

Tissue patterning is critical for the development and regeneration of organs. To advance the use of engineered reconstituted skin organs, we study cardinal features important for tissue patterning and hair regeneration. We find they spontaneously form spheroid configurations, with polarized epidermal cells coupled with dermal cells through a newly formed basement membrane.

Using Avian Skin Explants to Study Tissue Patterning and Organogenesis.

The developing avian skin during embryogenesis is a unique model that can provide valuable insights into tissue patterning. Here three variations on skin explant cultures to examine different aspects of skin development are described. First, ex vivo organ cultures and manipulations offer researchers opportunities to observe and study the development of feather buds directly.

The mechano-chemical circuit drives skin organoid self-organization.

Stem cells in organoids self-organize into tissue patterns with unknown mechanisms. Here, we use skin organoids to analyze this process. Cell behavior videos show that the morphological transformation from multiple spheroidal units with morphogenesis competence (CMU) to planar skin is characterized by two abrupt cell motility-increasing events before calming down.

Gap junctions in Turing-type periodic feather pattern formation.

Periodic patterning requires coordinated cell-cell interactions at the tissue level. Turing showed, using mathematical modeling, how spatial patterns could arise from the reactions of a diffusive activator-inhibitor pair in an initially homogenous two-dimensional field. Most activators and inhibitors studied in biological systems are proteins, and the roles of cell-cell interaction, ions, bioelectricity, etc.

Integrating Bioelectrical Currents and Ca Signaling with Biochemical Signaling in Development and Pathogenesis.

Roles of bioelectrical signals are increasingly recognized in excitable and nonexcitable non-neural tissues. Diverse ion-selective channels, pumps, and gap junctions participate in bioelectrical signaling, including those transporting calcium ions (Ca). Ca is the most versatile transported ion, because it serves as an electrical charge carrier and a biochemical regulator for multiple molecular binding, enzyme, and transcription activities.

Regional Specific Differentiation of Integumentary Organs: Regulation of Gene Clusters within the Avian Epidermal Differentiation Complex and Impacts of SATB2 Overexpression.

The epidermal differentiation complex (EDC) encodes a group of unique proteins expressed in late epidermal differentiation. The EDC gave integuments new physicochemical properties and is critical in evolution. Recently, we showed β-keratins, members of the EDC, undergo gene cluster switching with overexpression of SATB2 (Special AT-rich binding protein-2), considered a chromatin regulator.

Cyclic growth of dermal papilla and regeneration of follicular mesenchymal components during feather cycling.

How dermis maintains tissue homeostasis in cyclic growth and wounding is a fundamental unsolved question. Here, we study how dermal components of feather follicles undergo physiological (molting) and plucking injury-induced regeneration in chickens. Proliferation analyses reveal quiescent, transient-amplifying (TA) and long-term label-retaining dermal cell (LRDC) states.

Global feather orientations changed by electric current.

During chicken skin development, each feather bud exhibits its own polarity, but a population of buds organizes with a collective global orientation. We used embryonic dorsal skin, with buds aligned parallel to the rostral-caudal body axis, to explore whether exogenous electric fields affect feather polarity. Interestingly, brief exogenous current exposure prior to visible bud formation later altered bud orientations.

The Making of a Flight Feather: Bio-architectural Principles and Adaptation.

The evolution of flight in feathered dinosaurs and early birds over millions of years required flight feathers whose architecture features hierarchical branches. While barb-based feather forms were investigated, feather shafts and vanes are understudied. Here, we take a multi-disciplinary approach to study their molecular control and bio-architectural organizations.

Self-assembly of biological networks via adaptive patterning revealed by avian intradermal muscle network formation.

Networked structures integrate numerous elements into one functional unit, while providing a balance between efficiency, robustness, and flexibility. Understanding how biological networks self-assemble will provide insights into how these features arise. Here, we demonstrate how nature forms exquisite muscle networks that can repair, regenerate, and adapt to external perturbations using the feather muscle network in chicken embryos as a paradigm.

Instructive role of melanocytes during pigment pattern formation of the avian skin.

Animal skin pigment patterns are excellent models to study the mechanism of biological self-organization. Theoretical approaches developed mathematical models of pigment patterning and molecular genetics have brought progress; however, the responsible cellular mechanism is not fully understood. One long unsolved controversy is whether the patterning information is autonomously determined by melanocytes or nonautonomously determined from the environment.

Morpho-regulation in diverse chicken feather formation: Integrating branching modules and sex hormone-dependent morpho-regulatory modules.

Many animals can change the size, shape, texture and color of their regenerated coats in response to different ages, sexes, or seasonal environmental changes. Here, we propose that the feather core branching morphogenesis module can be regulated by sex hormones or other environmental factors to change feather forms, textures or colors, thus generating a large spectrum of complexity for adaptation. We use sexual dimorphisms of the chicken to explore the role of hormones.

Calcium oscillations coordinate feather mesenchymal cell movement by SHH dependent modulation of gap junction networks.

Collective cell migration mediates multiple tissue morphogenesis processes. Yet how multi-dimensional mesenchymal cell movements are coordinated remains mostly unknown. Here we report that coordinated mesenchymal cell migration during chicken feather elongation is accompanied by dynamic changes of bioelectric currents.

Transcriptome analyses of reprogrammed feather / scale chimeric explants revealed co-expressed epithelial gene networks during organ specification.

Background: The molecular mechanism controlling regional specific skin appendage phenotypes is a fundamental question that remains unresolved. We recently identified feather and scale primordium associated genes and with functional studies, proposed five major modules are involved in scale-to-feather conversion and their integration is essential to form today's feathers. Yet, how the molecular networks are wired and integrated at the genomic level is still unknown.

Comparative genomics and transcriptomics of Chrysolophus provide insights into the evolution of complex plumage coloration.

Background: As one of the most recognizable characteristics in birds, plumage color has a high impact on understanding the evolution and mechanisms of coloration. Feather and skin are ideal tissues to explore the genomics and complexity of color patterns in vertebrates. Two species of the genus Chrysolophus, golden pheasant (Chrysolophus pictus) and Lady Amherst's pheasant (Chrysolophus amherstiae), exhibit brilliant colors in their plumage, but with extreme phenotypic differences, making these two species great models to investigate plumage coloration mechanisms in birds.

Contraction of basal filopodia controls periodic feather branching via Notch and FGF signaling.

Branching morphogenesis is a general mechanism that increases the surface area of an organ. In chicken feathers, the flat epithelial sheath at the base of the follicle is transformed into periodic branches. How exactly the keratinocytes are organized into this pattern remains unclear.

Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis.

Cutaneous wounds in adult mammals typically heal by scarring. However, large full-thickness wounds undergo wound-induced hair follicle neogenesis (WIHN), a form of regeneration. Here, we show that WIHN requires transient expression of epidermal Msx2 in two phases: the wound margin early and the wound center late.

MicroCT Imaging on Living Alligator Teeth Reveals Natural Tooth Cycling.

To study tooth cycling in polyphyodont animals, we chose to work on alligators. Alligators have teeth in three phases of development at each tooth location. This assembly of three teeth is called a tooth family unit.

Systems Biology Analyses in Chicken: Workflow for Transcriptome and ChIP-Seq Analyses Using the Chicken Skin Paradigm.

With advances in molecular biology, various biological phenomena can now be explored at higher resolution using mRNA sequencing (RNA-Seq) and chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq), two powerful high-throughput next-generation sequencing (NGS) technologies. While methods are used widely in mouse, human, etc., less information is available in other animals, such as the chicken.

Self-organization process in newborn skin organoid formation inspires strategy to restore hair regeneration of adult cells.

Organoids made from dissociated progenitor cells undergo tissue-like organization. This in vitro self-organization process is not identical to embryonic organ formation, but it achieves a similar phenotype in vivo. This implies genetic codes do not specify morphology directly; instead, complex tissue architectures may be achieved through several intermediate layers of cross talk between genetic information and biophysical processes.

Topographical mapping of α- and β-keratins on developing chicken skin integuments: Functional interaction and evolutionary perspectives.

Avian integumentary organs include feathers, scales, claws, and beaks. They cover the body surface and play various functions to help adapt birds to diverse environments. These keratinized structures are mainly composed of corneous materials made of α-keratins, which exist in all vertebrates, and β-keratins, which only exist in birds and reptiles.

The Modulatable Stem Cell Niche: Tissue Interactions during Hair and Feather Follicle Regeneration.

Hair and feathers are unique because (1) their stem cells are contained within a follicle structure, (2) they undergo cyclic regeneration repetitively throughout life, (3) regeneration occurs physiologically in healthy individuals and (4) regeneration is also induced in response to injury. Precise control of this cyclic regeneration process is essential for maintaining the homeostasis of living organisms. While stem cells are regulated by the intra-follicle-adjacent micro-environmental niche, this niche is also modulated dynamically by extra-follicular macro-environmental signals, allowing stem cells to adapt to a larger changing environment and physiological needs.