Conrad Hal Waddington was a British developmental biologist who mainly worked in Cambridge and Edinburgh, but spent the late 1930s with Morgan in California learning about Drosophila. He was the first person to realize that development depended on the then unknown activities of genes, and he needed an appropriate model organism. His major experimental contributions were to show how mutation analysis could be used to investigate developmental mechanisms in Drosophila, and to explore how developmental mutation could drive evolution, his other (...) deep interest. Waddington was, however, predominantly a thinker, and set out to provide a coherent framework for understanding the genetic bases of embryogenesis and evolution, developing his ideas in many books. Perhaps his best-known concept is the epigenetic landscape: here a ball rolls down a complex valley, making path choices. The rolling ball represents a cell’s development over time, while the topography represents the changing regulatory environment that controls these choices. In its later forms, the role of each feature in the landscape was controlled by the effects of sets of interacting genes, an idea underpinning contemporary approaches to systems biology. Waddington was the first developmental geneticist and probably the most important developmental biologist of the pre-molecular age. (shrink)

In 2011, Peterson suggested that the main reason why C.H. Waddington was essentially ignored by the framers of the modern evolutionary synthesis in the 1950s was because they were Cartesian reductionists and mathematical population geneticists while he was a Whiteheadian organicist and experimental geneticist who worked with Drosophila. This paper suggests a further reason that can only be seen now. The former defined genes and their alleles by their selectable phenotypes, essentially the Mendelian view, while Waddington defined a gene through (...) its functional role as determined by genetic analysis, a view that foresaw the modern view that a gene is a DNA sequence with some function. The former were interested in selection, while Waddington focused on variation. The differences between the two views of a gene are briefly considered in the context of systems biology. (shrink)

Because the kidney (metanephros) starts to function before completing development, its patterning and morphogenesis need to be closely integrated with its growth. This is achieved by blast cells at the kidney periphery generating new nephrons that link up to the extending collecting‐duct arborisation, while earlier‐formed and more internal nephrons are maturing and beginning to filter serum. This pattern of development requires that cell division and apoptosis be co‐ordinated in the various kidney compartments (collecting‐ducts, blast cells, metanephric mesenchyme, nephrons and vascular (...) system). The underlying regulatory networks for cell proliferation are beginning to be unravelled, mainly through expression studies, mutation analysis and experimentation in vitro. This article summarises current knowledge of kidney growth and apoptosis, and analyses some of the 80 or so ligand–receptor pairings that seem to sustain development and growth. It also points to some unanswered questions, the most intriguing being what role does apoptosis play during normal kidney development? BioEssays 24:72–82, 2002. © 2002 John Wiley & Sons, Inc. (shrink)

Although the segregation of mesenchyme into distinct aggregates is the first step in the development of a range of tissues that includes bones, somites, feathers and nephrons, we still know very little about the mechanisms by which this happens. There are two obvious types of explanation: first, that there are global pre‐patterns within the mesenchyme whose molecular expression leads to tissue fragmentation and, second, that the condensations arise spontaneously through the local morphogenetic abilities of the cells. The only known mechanism (...) for the latter possibility is cell traction and this paper suggests that current studies are compatible with traction playing a primary role in the formation of nephrogenic condensations in the developing kidney and the separation of somites, but not for the generation of feather rudiments where there is evidence of a prepattern of adhesivity. (shrink)