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Biomedical subjects

L Wolpert

Publications and source records attributed to L Wolpert.

At least 19 recordsLinked to original sources
PubMed1992

Development of left/right handedness in the chick heart.

The chick heart tube develops from the fusion of the right and left areas of precardiac mesoderm and in almost all cases loops to the embryo's right-hand side. We have investigated whether any intrinsic difference exists in the right and left areas of precardiac mesoderm, that influences the direction of looping of the heart tube. Chick embryos incubated to stages 4,5 and 6 were cultured by the New method. Areas of precardiac mesoderm were exchanged between donor and host embryos of the same stage and different stages to form control, double-right and double-left sided embryos. Overall, double-right sided embryos formed many more left-hand loops than double-left sided embryos. At stages 4 and 5 a small percentage of double-right embryos formed left-hand loops (13%) whereas at stage 6 almost 50% of hearts had left-hand loops. Control embryos formed right-hand loops in 97% of cases. The stability of right-hand heart looping by double-left sided embryos, may be related to the process of 'conversion', whereas the direction of looping by double-right sided embryos has become randomised. There is some indication that an intrinsic change occurred in the precardiac mesoderm between stages 5 and 6 that later influenced the direction of looping of the heart tube. The direction of body turning is suggested to be linked to the direction of heart looping.

Animals↗
PubMed1992

Gastrulation and the evolution of development.

The original eukaryotic cell may have possessed the key processes necessary for metazoan development--cell differentiation, patterning and motility--and these are present in the cell cycle. Protozoa also possess key patterning processes. It remains a problem as to why there should be two main modes of development--one based on asymmetric cell division and the other on cellular interactions. The latter may be related to asexual reproduction. The morphogenetic movements of gastrulation--as distinct from specifying the body plan--are highly conserved in a wide variety of organisms. This may reflect the requirement for patterning being specified in two dimensions, sheets of cells, and a third dimension being created by cell infolding. The origin of the gastrula can be accounted for in terms of Haeckel's gastrea theory--an early metazoan resembling the gastrula. Gastrulation in Cnidaria may resemble the primitive condition but there is nevertheless considerable diversity. While this may reflect, for example, yolkiness, it seems that there is little selection on developmental processes other than for reliability. Thus it is possible that the embryo is privileged with respect to selection and this may help account for the evolution of novel processes like the origin of the neural crest. Reliability is the key demand made on development. This may be provided by apparent redundancy. Since many developmental processes involve switches and spatial patterning reliability is provided by parallel buffering mechanisms and not by negative feedback.

Animals↗
PubMed1991

Expression of the homeobox Hox-4 genes and the specification of position in chick wing development.

The chicken Hox-4 homeogenes, like those of the mouse, are coordinately expressed in partially overlapping domains during wing development. Local application of retinoic acid, a putative endogenous morphogen, induces de novo transcription of Hox-4 genes. The mirror-image patterns of Hox-4 gene expression, which are obtained in this way, correlate with the subsequent development of mirror-image patterns of digits. Hox-4 genes probably encode positional information.

Amino Acid Sequence↗
PubMed1991

Development of handed body asymmetry in mammals.

We have proposed a three step model for the specification of left-right in mammalian embryos. The fundamental assumption is that handedness is imparted by an asymmetrical molecule. Conversion of molecular asymmetry to the cellular level gives a property to one side of the embryo to bias an otherwise random generation of an asymmetrical gradient which can be interpreted by developing organs. Rat embryos, treated at discrete stages, show a window of sensitivity for disruption of handedness, which may reflect the time of conversion/biasing. Heat shock and several chemicals cause left-right inversion in up to 50% of embryos exposed during neural groove formation. Earlier stages are less sensitive; no treatment begun after foregut pocket formation influences asymmetry. Evidence for cellular interactions in left-right specification comes from the apparent rescue of iv/iv mutant embryos in chimeras. We are looking for molecular left-right disparity before morphological asymmetry but detect no differences in two-dimensional protein profiles. Using an indirect measure, we find a right-left gradient of tissue oxygen in embryos at the 20-30 somite stage. This may reflect asymmetrical vasculature, as we have suggested to explain drug-induced asymmetrical limb malformations.

Animals↗
PubMed1979

The effect of cell killing by x-irradiation on pattern formation in the chick limb.

It has been suggested that positional information along the proximo-distal axis of the limb-bud is specified by time spent in the progress zone. Mesenchyme cells have been killed by X-irradiation, reducing the rate cells leave the zone. The time spent there by some cells is thus increased. When limbs, stage 18/19, stage 21, or tips of stage 24, are treated with increasing doses of X-irradiation, from 1000 rads to 2500 rads proximal structures are progressively lost, whereas distal ones--the digits--are relatively unaffected. There was no evidence for intercalation of missing parts. These effects are due to killing or damage of mesenchyme cells: the ectoderm is not affected at these doses. The results are consistent with a quantitative analysis based on the progress zone model, in which viable cells repopulate the progress zone and gradually restore it to normal as non-dividing cells are diluted out. It is suggested that any treatment causing damage to the mesenchyme at early stages will give similar results. The mesenchyme cells appear to be surprisingly resistant to radiation damage. The form of the limb-bud is not altered by damaging the mesenchyme. Differences in the development of structures at similar proximo-distal levels, following irradiation, is considered in terms of the requirement of a threshold number of cells.

Abnormalities, Radiation-Induced↗
PubMed1979

Somite formation in the early chick embryo following grafts of Hensen's node.

Quail grafts of Hensen's node were examined for their potential to induce somites in chick blastoderms. The origin of the structures induced depended on the distance of the graft from the host's midline. Nodes placed at the margin of the area pellucida resulted in structures differentiated from the cells of the graft, whereas medially the graft organized host cells to form rows of somites. The results are discussed in terms of competence of graft and host mesenchyme and a positional signal from the node.

Animals↗
PubMed1978

Cell contacts and sorting out in vivo: the behaviour of some embryonic tissues implanted into the developing chick wing.

The interaction of cells from embryonic liver, neural retina and mesonephros with cells from limb-bud mesenchyme has been investigated in vivo by grafting these tissues into the developing chick wing-bud. The implanted cells were in all cases from quail tissue which can be recognized histologically. As embryonic liver and neural tube are tissues that sort externally to limb-bud mesenchyme in mixed aggregates, it would be expected, from a differential adhesiveness hypothesis, that heterotypic adhesions along the borders of graft and host would be favoured over cell-cell adhesions in the graft. No morphological signs of this were evident: rather the grafted cells maximized like-like contacts. The cells of the grafts, including those from control mesenchyme, did not invade into the wing. The results were the same irrespective of whether the graft was a fragment of tissue or a pellet of reaggregated cells. This supports the idea that cells within tissues are not actively moving around and also provides controls for assaying the invasiveness of other cell types, such as malignant cells into the wing.

Animals↗
PubMed1978

The development of the pattern of growth.

It is proposed that the varying patterns of growth in development can be viewed as an aspect of pattern formation, and that different growth programmes are specified at an early stage. This is illustrated largely with respect to the development and growth of the chick wing. The spatial pattern of cellular differentiation and programme for growth can be considered in terms of the concept of positional information. The lengths of the cartilaginous elements are determined by the initial length of the primordium and its later growth, involving cell multiplication enlagement and matrix secretion. It seems that tissues have a high degree of autonomy with respect to differentiation and growth after they have had their position specified. The cellular basis of programmed growth is discussed.

Animals↗