J. C. McLachlan

Cartilaginous development of the human craniovertebral junction as visualised by a new three-dimensional computer reconstruction technique

Serial transverse histological sections of the human craniovertebral junction (CVJ) of 4 normal human embryos (aged 45 to 58 d) and of a fetus (77 d) were used to create 3‐dimensional computer models of the CVJ. The main components modelled included the chondrified basioccipital, atlas and axis, notochord, the vertebrobasilar complex and the spinal cord. Chondrification of the component parts of CVJ had already begun at 45 d (Stage 18). The odontoid process appeared to develop from a short eminence of the axis forming a third occipital condyle with the caudal end of the basioccipital. The cartilaginous anterior arch of C1 appeared at 50–53 d (Stages 20–21). Neural arches of C1 and C2 showed gradual closure, but there was still a wide posterior spina bifida in the oldest reconstructed specimen (77 d fetus). The position of the notochord was constant throughout. The normal course of the vertebral arteries was already established and the chondrified vertebral foramina showed progressive closure. The findings confirm that the odontoid process is not derived solely from the centrum of C1 and that there is a ‘natural basilar invagination’ of C2 during normal embryonic development. On the basis of the observed shape and developmental pattern of structures of the cartilaginous human CVJ, we suggest that certain pathologies are likely to originate during the chondrification phase of development.

Marks, scores and grades: scaling and aggregating student assessment outcomes

The term marks conflates the concepts of scores (raw test performance) and grades (level of performance). Neither scores nor grades represent interval scales, and therefore properly speaking arithmetic means should not be calculated during aggregation. The distributions of scores from a variety of kinds of assessment are considered, and ways of converting scores to grades are discussed. Methods of aggregation are also considered, and several strategies for implementing these via spreadsheets are made available.

The vomeronasal organ in the human embryo, studied by means of three-dimensional computer reconstruction

The human vomeronasal organ is of interest because of its potential role in sex pheromone detection. Due to the scarcity of early human material, studies of its development have concentrated on fetal rather than embryonic stages. The availability of embryonic specimens in the Walmsley Collection has enabled us to study the development of the vomeronasal organ (VNO) in human embryos between Carnegie Stages 17 and 23. Embryos at Carnegie Stage 17 or below showed no evidence of a VNO. One embryo with characteristics intermediate between Carnegie stages 17 and 18 was the earliest to show evidence of a VNO, in the form of a shallow indentation. All embryos at Carnegie Stages 18 or later had VNOs. Three‐dimensional computer reconstructions were made of the VNO in each specimen where this was possible. This in part depended on the plane of section. The total volume and lumen volume were measured from these reconstructions and the volume of the vomeronasal epithelium was calculated by subtraction. A generally consistent increase in total volume and epithelial volume was observed with increasing developmental stage. The lumen contributed rather little to the total volume at these stages.

Short Report. The study of early human embryos using interactive 3-dimensional computer reconstructions

Tracings of serial histological sections from 4 human embryos at different Carnegie stages were used to create 3‐dimensional (3D) computer models of the developing heart. The models were constructed using commercially available software developed for graphic design and the production of computer generated virtual reality environments. They are available as interactive objects which can be downloaded via the World Wide Web. This simple method of 3D reconstruction offers significant advantages for understanding important events in morphological sciences.

Computer-aided interactive three-dimensional reconstruction of the embryonic human heart

Despite the fact that development of the human embryo heart is of considerable clinical importance, there is still disagreement over the process and the timing of events. It is likely that some of the conflicting accounts may have arisen from difficulties in describing and visualising 3‐dimensional structures from 2‐dimensional sections. To help overcome this problem and to improve our understanding of the development of the heart, we have devised techniques for the production of interactive 3D models reconstructed from serial histological sections of human embryos. Our method uses commercial software designed for the creation of 3D models and virtual reality environments. The ability to construct interactive visual images which both illustrate and communicate complex 3D information contributes to our understanding of the complex developmental changes occurring in embryogenesis.

Correspondence: World Wide Web access to the British Universities Human Embryo Database

The British Universities Human Embryo Database has been created by merging information from the Walmsley Collection of Human Embryos at the School of Biological and Medical Sciences, University of St Andrews and from the Boyd Collection of Human Embryos at the Department of Anatomy, University of Cambridge. The database has been made available electronically on the Internet and World Wide Web browsers can be used to implement interactive access to the information stored in the British Universities Human Embryo Database. The database can, therefore, be accessed and searched from remote sites and specific embryos can be identified in terms of their location, age, developmental stage, plane of section, staining technique, and other parameters. It is intended to add information from other similar collections in the UK as it becomes available.

Direct demonstration of production of transforming growth factor activity by embryonic chick tissue.

The presence of transforming growth factor activity in early chick embryos was directly demonstrated by the ability of limb and tail buds to induce anchorage independent division in NRK 49f cells. Colony number increased with limb bud number and developmental stage. Medium conditioned by tail buds contained some stimulating effect, and strongly promoted the action of other transforming growth factors.

A proximo-distal gradient of FGF-like activity in the embryonic chick limb bud

Abstract. In a microassay for anchorage-independent growth in soft agar, NR6 cells form colonies in a dose-dependent manner in the presence of fibroblast growth factor (FGF). Using this assay system, the ability of thin sequential slices of embryonic chick limb bud to promote colony formation was investigated. A functional gradient of colony-promoting ability along the proximo-distal axis of the developing chick limb bud (stages 22–26) was observed. The highest number of colonies was observed in the presence of the most distal slices, and colony number decreased progressively at proximal levels. This gradient was specifically eliminated by the addition of anti-FGF antibody to the assay, indicating that it was caused by a functional gradient of an FGF-like molecule. Limbs of stages 21–26 were assayed: before this time limb buds are too small to slice in the proximo-distal axis in the required manner. The FGF-like gradient was observed at stages 22 to 26.

Growth Factors Produced by the Polarising Zone — A Complement to the Retinoic Acid System

After a ZPA graft to the limb anterior margin, the limb bud becomes wider, and the resulting reduplicated limbcontains many more cells than a comparable control (Smith and Wolpert, 1981). This indicates that the ZPA has initiated growth in the host limb. This effect can also be observed at the cellular level, in that cells close to a ZPA graftshow an increased labelling index compared to controls (Cooke and Summerbell, 1980). Such a growth promoting effect might be at least formally separable from the reduplicating effect of the ZPA, and it is certainly more amenable to quantitative analysis in vitro. We have therefore been engaged in investigating the mitogenic effect of ZPAs in culture by a number of different techniques, including time lapse video recording, and uptake of tritiated thymidine as detected both by scintillation counting and by auto-radiography. Although each of these methods may present special problems, in general we detect good concordance between the different techniques.

A microwell assay for anchorage independent cell growth

We describe modifications of the conventional assay for anchorage independent growth of fibroblasts that enable the assay to be carried out in microwell plates, as opposed to the conventional Petri dishes. The microwell assay is a good discriminator of final EGF concentrations in the range 10-100 picograms/ml, and can be used to detect absolute amounts of EGF below 2 pg. Addition of TGF beta to EGF enhances colony formation in the microassay in the usual manner. We describe the use of this microassay to identify and map local production of transforming growth factor activity by the component pieces of individual chick embryos. Transforming activity was identified in all the stages tested (Hamburger and Hamilton stages 13-23). Highest levels were found near the mid-line of the embryo. No clear differences in the cranio-caudal axis have so far been identified. This technique will enable the spatial and temporal distribution of transforming activity throughout vertebrate embryos to be completely mapped. It seems likely that this mapping process will help elucidate the normal role of transforming growth factors in embryos.