The three fields emerged from an unusual concentration

in space and time of a handful of seminal experimental observations. In just a few years, we learned that heterotopic transplantation of transitional epithelium into skeletal muscle induces heterotopic bone formation [1]; that heterotopic transplants of bone marrow also do so [[2] and [3]], but that the two phenomena are radically distinct from one another: the former is dependent on the release of a soluble factor, while the latter is not. Identification of BMPs [[4], [5], [6] and [7]] and perisinusoidal reticular cells as the specific factor and cell type generating bone in heterotopic transplants of transitional PD-0332991 cell line epithelium and bone marrow, respectively, selleck products represents the ending point of two long and diverging journeys that originated from those seminal experiments. Likewise, the definition of the bone marrow microenvironment as the host of signals provided by stromal cells and required for hematopoiesis, and the pursuit of a “niche” for hematopoietic stem cells proper represent the developments over time of a third seminal observation; that is, that grafting of bone

marrow in closed systems (diffusion chambers) would generate bone but bar the development of hematopoiesis, whereas transplantation in open systems would allow for both bone formation and development of marrow [2]. That all of these fundamental observations, which not only withstood the test of time, but also represented the seed for the subsequent flourishing of major fields of investigation, arose from the practice of heterotopic transplantation cannot escape notice. Considering the tremendous impact of establishing quail–chick chimeras (a kind of heterotopic transplantation in embryos) [8] and [9]in developmental

Cytidine deaminase biology and how much it contributed to further developments in lineage tracing, one is tempted by foolishly wondering what magic is inherent in putting tissues and cells where they do not belong (ectopic transplantation), and why is this practice so instructive. Perhaps all this simply highlights the fundamental link between space (and time) and development (lineage, commitment, differentiation), a notion we owe, ultimately, to Alan Turing (the father, among many other things, of the diffusion–reaction model which established the chemical basis of morphogenesis [10]), and before him, to D’Arcy Thompson (a classicist and a morphologist renowned for his attention to the physical and mathematical laws underpinning morphogenesis) [11].