'Neighbourhood watch' model: embryonic epiblast cells assess positional information in relation to their neighbours.

In many developing and regenerating systems, tissue pattern is established through gradients of informative morphogens, but we know little about how cells interpret these. Using experimental manipulation of early chick embryos, including misexpression of an inducer (VG1 or ACTIVIN) and an inhibitor (BMP4), we test two alternative models for their ability to explain how the site of primitive streak formation is positioned relative to the rest of the embryo. In one model, cells read morphogen concentrations cell-autonomously.

From soil mechanics to chick development.

Here, I provide some recollections of my life, starting as a civil engineer in South Africa and how I gradually became interested in biology, particularly pattern formation. In retrospect, I think that my decision to work on chick embryos to study limb development back in 1966 turned out to be the right one. The principles discovered in these 50 years, both by my collaborators and by other colleagues, have established the principles of how the limb develops in higher vertebrates, including humans.

Positional Information and Pattern Formation.

The concept of positional information proposes that cells acquire positional values as in a coordinate system, which they interpret by developing in particular ways to give rise to spatial patterns. Some of the best evidence for positional information comes from regeneration experiments, and the patterning of the leg and antenna in Drosophila, and the vertebrate limb. Central problems are how positional information is set up, how it is recorded, and then how it is interpreted by the cells.

Perspective.

I am a developmental biologist, but I started off as a civil engineer. I did some research on soil mechanics but decided to change to biology. A friend changed my life when he told me about the mechanics of cell division, on which I did my PhD at Kings College.

An interview with Lewis Wolpert.

Lewis Wolpert is a retired developmental biologist who, over his long career, has made many important contributions to the field, from his French Flag model and the concept of positional information to the famous quote that it is "not birth, marriage or death, but gastrulation which is truly the most important time in your life." In addition to his scientific contributions, Lewis is also a prolific writer, from the textbook 'Developmental Biology' to books about popular science, religion and his battle with depression. Although born in South Africa, it was in the United Kingdom that Lewis spent most of his scientific career.

Gradients of signalling in the developing limb.

The developing limb is one of the first systems where it was proposed that a signalling gradient is involved in pattern formation. This gradient for specifying positional information across the antero-posterior axis is based on Sonic hedgehog signalling from the polarizing region. Recent evidence suggests that Sonic hedgehog signalling also specifies positional information across the antero-posterior axis by a timing mechanism acting in parallel with graded signalling.

Positional information and patterning revisited.

The concept of positional information proposes that cells acquire positional values as in a coordinate system, which they interpret by developing in particular ways to give rise to spatial patterns. Some of the best evidence for positional information comes from regeneration experiments, and the patterning of the leg and antenna in Drosophila and the vertebrate limb. Central problems are how positional information is set up, how it is recorded, and then how it is interpreted by the cells.

There is no place for the psychoanalytic case report in the British Journal of Psychiatry.

As evidence-based mental health and the randomised controlled trial come to dominate the content of major psychiatric journals, the status and clinical utility of single case reports have been increasingly questioned. Arguably, owing to their subjective, anecdotal nature and unsuitability for rigorous scientific testing, this is particularly true of psychoanalytic case studies. Professor Peter Fonagy and Professor Lewis Wolpert debate here whether or not there is a place for such case reports in the British Journal of Psychiatry.

Diffusible gradients are out - an interview with Lewis Wolpert. Interviewed by Richardson, Michael K.

In 1969, Lewis Wolpert published a paper outlining his new concepts of "pattern formation" and "positional information". He had already published research on the mechanics of cell membranes in amoebae, and a series of classic studies of sea urchin gastrulation with Trygve Gustavson. Wolpert had presented his 1969 paper a year earlier at a Woods Hole conference, where it received a very hostile reception: "I wasnt asked back to America for many years!".

Depression in an evolutionary context.

Sadness and low levels of depression are adaptive since they lead the individual to try and make up a loss. By contrast, severe or clinical depression is not adaptive, but can be thought of as sadness having become malignant.

The amniote primitive streak is defined by epithelial cell intercalation before gastrulation.

During gastrulation, a single epithelial cell layer, the ectoderm, generates two others: the mesoderm and the endoderm. In amniotes (birds and mammals), mesendoderm formation occurs through an axial midline structure, the primitive streak, the formation of which is preceded by massive 'polonaise' movements of ectoderm cells. The mechanisms controlling these processes are unknown.

Specifying positional information in the embryo: looking beyond morphogens.

Concentration gradients of small diffusible molecules called morphogens are key regulators of development, specifying position during pattern formation in the embryo. It is now becoming clear that additional or alternative mechanisms involving interactions among cells are also crucial for positional specification.

Head-tail patterning of the vertebrate embryo: one, two or many unresolved problems?

When, where and how is the head-tail axis of the embryo set up during development? These are such fundamental and intensely studied questions that one might expect them to have been answered long ago. Not so; we still understand very little about the cellular or molecular mechanisms that lead to the orderly arrangement of body elements along the head-tail axis in vertebrates. In this paper, we outline some of the major outstanding problems and controversies and try to identify some reasons why it has been so difficult to resolve this important issue.

The Medawar Lecture 1998 is science dangerous?

The idea that science is dangerous is deeply embedded in our culture, particularly in literature, yet science provides the best way of understanding the world. Science is not the same as technology. In contrast to technology, reliable scientific knowledge is value-free and has no moral or ethical value.

Much more from the chicken's egg than breakfast--a wonderful model system.

The chick embryo has played a major role in the advance of our understanding of embryonic development. It has been particularly helpful in relation to amniotes like the mouse, for unlike the mouse in the early embryo the epiblast is beautifully flat, while in the mouse it is all curled up. Here I briefly describe some history and a few of the major achievements that came from the chick embryo.

Determination of embryonic polarity in a regulative system: evidence for endogenous inhibitors acting sequentially during primitive streak formation in the chick embryo.

Avian embryos have a remarkable capacity to regulate: when a pre-primitive streak stage embryo is cut into fragments, each fragment can spontaneously initiate formation of a complete embryonic axis. We investigate the signalling pathways that initiate primitive streak formation and the mechanisms that ensure that only a single axis normally forms. As reported previously, an ectopic primitive streak can be induced by misexpression of Vg1 in the marginal zone.

Lewis Wolpert discusses development and depression. Interview by Joanne Clough.

Lewis Wolpert is Professor of Biology as Applied to Medicine in the Department of Anatomy and Developmental Biology at University College, London, UK. His research interests focus on the mechanisms that are involved in embryonic development. Lewis originally trained as a civil engineer in South Africa but in 1955 made the move to research in cellular biology at King's College, London.