Biomedical subjects

B Frank Eames

Publications and source records attributed to B Frank Eames.

4 recordsLinked to original sources

PubMed2005

Quail-duck chimeras reveal spatiotemporal plasticity in molecular and histogenic programs of cranial feather development.

The avian feather complex represents a vivid example of how a developmental module composed of highly integrated molecular and histogenic programs can become rapidly elaborated during the course of evolution. Mechanisms that facilitate this evolutionary diversification may involve the maintenance of plasticity in developmental processes that underlie feather morphogenesis. Feathers arise as discrete buds of mesenchyme and epithelium, which are two embryonic tissues that respectively form dermis and epidermis of the integument. Epithelial-mesenchymal signaling interactions generate feather buds that are neatly arrayed in space and time. The dermis provides spatiotemporal patterning information to the epidermis but precise cellular and molecular mechanisms for generating species-specific differences in feather pattern remain obscure. In the present study, we exploit the quail-duck chimeric system to test the extent to which the dermis regulates the expression of genes required for feather development. Quail and duck have distinct feather patterns and divergent growth rates, and we exchange pre-migratory neural crest cells destined to form the craniofacial dermis between them. We find that donor dermis induces host epidermis to form feather buds according to the spatial pattern and timetable of the donor species by altering the expression of members and targets of the Bone Morphogenetic Protein, Sonic Hedgehog and Delta/Notch pathways. Overall, we demonstrate that there is a great deal of spatiotemporal plasticity inherent in the molecular and histogenic programs of feather development, a property that may have played a generative and regulatory role throughout the evolution of birds.

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PubMed2004

Hierarchy revealed in the specification of three skeletal fates by Sox9 and Runx2.

Across vertebrates, there are three principal skeletal tissues: bone, persistent cartilage, and replacement cartilage. Although each tissue has a different evolutionary history and functional morphology, they also share many features. For example, they function as structural supports, they are comprised of cells embedded in collagen-rich extracellular matrix, and they derive from a common embryonic stem cell, the osteochondroprogenitor. Occasionally, homologous skeletal elements can change tissue type through phylogeny. Together, these observations raise the possibility that skeletal tissue identity is determined by a shared set of genes. Here, we show that misexpression of either Sox9 or Runx2 can substitute bone with replacement cartilage or can convert persistent cartilage into replacement cartilage and vice versa. Our data also suggest that these transcription factors function in a molecular hierarchy in which chondrogenic factors dominate. We propose a binary molecular code that determines whether skeletal tissues form as bone, persistent cartilage, or replacement cartilage. Finally, these data provide insights into the roles that master regulatory genes play during evolutionary change of the vertebrate skeleton.

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PubMed2004

Conserved molecular program regulating cranial and appendicular skeletogenesis.

The majority of in vivo studies on bone and cartilage differentiation are carried out using the appendicular skeleton as a model system, with the implicit assumption that skeletal formation is equivalent throughout the body. This assumption persists, despite differences in the cellular origins of the skeletogenic precursors. To test the hypothesis that a fundamental set of genes directs skeletal cell differentiation throughout the body, we analyzed cartilage and bone of the chick limb and head during mesenchymal condensation, and when the skeletal tissues had matured. First, we analyzed the expression patterns of transcription factors in early skeletogenic condensations, which revealed similarities among skeletal cell specification in the limb and head. For example, skeletogenic condensations that undergo endochondral ossification had equivalent expression patterns of skeletogenic transcription factors in both limb and head. In the head, many elements also differentiate through intramembranous ossification, or through persistent cartilage formation. Our analyses of these skeletogenic condensations revealed that a unique expression pattern of transcription factors distinguishes among three skeletal tissue fates. The vasculature was excluded from all three skeletogenic condensations, demonstrating that this is not a characteristic unique to endochondral ossification. Second, we compared three different types of more mature cartilage and bone tissue in both the limb and the head, by analyzing a variety of skeletal collagens and signaling molecules. Histological and molecular markers of cartilage and bone generally were conserved between the limb and head skeletons, although we uncovered subtle differences in signaling pathways that might influence cranial and appendicular skeletogenesis.

Animals↗

PubMed2003

Molecular ontogeny of the skeleton.

From a traditional viewpoint, skeletal elements form by two distinct processes: endochondral ossification, during which a cartilage template is replaced by bone, and intramembranous ossification, whereby mesenchymal cells differentiate directly into osteoblasts. There are inherent difficulties with this historical classification scheme, not the least of which is that bones typically described as endochondral actually form bone through an intramembranous process, and that some membranous bones may have a transient chondrogenic phase. These innate contradictions can be circumvented if molecular and cellular, rather than histogenic, criteria are used to describe the process of skeletal tissue formation. Within the past decade, clinical examinations of human skeletal syndromes have led to the identification and subsequent characterization of regulatory molecules that direct chondrogenesis and osteogenesis in every skeletal element of the body. In this review, we survey these molecules and the tissue interactions that may regulate their expression. What emerges is a new paradigm, by which we can explain and understand the process of normal- and abnormal-skeletal development.

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