Formation of branching epithelial trees from unbranched precursors is a common process in animal organogenesis. In humans, for example, this process gives rise to the airways of the lungs, the urine‐collecting ducts of the kidneys and the excretory epithelia of the mammary, prostate and salivary glands. Branching in these different organs, and in different animal classes and phyla, is morphologically similar enough to suggest that they might use a conserved developmental programme, while being dissimilar enough not to make it obviously (...) certain that they do. In this article, I review recent discoveries about the molecular regulation of branching morphogenesis in the best‐studied systems, and present evidence for and against the idea of there being a highly conserved mechanism. Overall, I come to the tentative conclusion that key mechanisms are highly conserved, at least within vertebrates, but acknowledge that more work needs to be done before the case is proved beyond reasonable doubt. BioEssays 24:937–948, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Much contemporary biology consists of identifying the molecular components that associate to perform biological functions, then discovering how these functions are controlled. The concept of control is key to biological understanding, at least of the physiological kind; identifying regulators of processes underpins ideas of causality and allows complicated, multicomponent systems to be summarized in relatively simple diagrams and models. Unfortunately, as this article demonstrates by drawing on published articles, there is a growing tendency for authors to claim that a molecule (...) is a ‘regulator’ of something on evidence that cannot support the conclusion. In particular, gene knockout experiments, which can demonstrate only that a molecule is necessary for a process, are all too frequently being misinterpreted as revealing regulation. This logical error threatens to blur the important distinction between regulation and mere necessity and therefore to weaken one of our strongest tools for comprehending how organisms work. (shrink)

There is now a rapidly expanding population of interlinked developmental biology databases on the World Wide Web that can be readily accessed from a desk‐top PC using programs such as Netscape or Mosaic. These databases cover popular organisms (Arabidopsis, Caenorhabditis, Drosophila, zebrafish, mouse, etc.) and include gene and protein sequences, lists of mutants, information on resources and techniques, and teaching aids. More complex are databases relating domains of gene expression to embryonic anatomy and these range from existing text‐based systems for (...) specific organs such as kidney, to a massive project under development, that will cover gene expression during the whole of mouse embryogenesis. In this brief article, we review selected examples of databases currently available, look forward to what will be available soon, and explain how to gain access to the World Wide Web. (shrink)

Epithelia can be defined morphologically as tissues that line surfaces, and ultrastructurally with reference to their cells' apico‐basal polarity and possession of specific cell‐cell junctions. Defining the epithelial phenotype at a molecular level is more problematic ‐ while it is easy to name proteins (e.g. keratins) expressed by a “typical” epithelium, no known molecules are expressed by every epithelium but by no other tissues. Cells can differentiate to and from the epithelial state as part of normal development, as a response (...) to disease or when manipulated in culture. Many factors (matrix components, adhesion molecules, growth factors, transcription factors) have been identified that can trigger these transitions of phenotype in specific cases, but to date no general master regulators of the epithelial state have been found. The epithelial state may therefore be controlled by multiple regulatory genes so that there is no single molecule responsible for all of the diverse types of epithelium that exist in higher animals. (shrink)

Branching morphogenesis of epithelia is an important mechanism in mammalian development. The last decade has seen the identification of many signalling pathways and intracellular mechanisms that control epithelial branching. Tissue‐level mechanisms that space new branches out have, however, remained an unsolved problem. A recent publication by Nelson et al.1 suggests—if extrapolation from their novel and abstract culture system is valid—that branches may be spaced out by a system of mutual inhibition based on diffusion of TGFβ. Such a system would allow (...) a developing tree to arrange itself, without detailed genetic specification, by adaptive self‐organization. BioEssays 29: 205–207, 2007. © 2007 Wiley Periodicals, Inc. (shrink)