The organizer concept and modern embryology: Anglo-American perspectives.

This paper analyses the origins of the Spemann-Mangold organizer concept of 1924 in relation to his earlier background and concepts. It traces the consequences and fate of the organizer, and related concepts (embryonic induction, gradients, fields) through subsequent phases in the evolution of developmental biology up to the present, primarily from a UK perspective, but also in the USA. The origins of Wolpert's concept of positional information of around 1970 are analysed; this markedly different model of embryogenesis effectively took the place of the organizer, following on from a generally assumed out-datedness of the corpus of Spemann's data and concepts. Explanations in terms of historical forces are suggested; events are seen as a historical causal chain. A crucial factor appears to have been the long-term neglect of morphogenetic cell movement as an integral component of an adequate induction-based model. The paper discusses the general inter-relation of history and science, and particularly the implications for current scientific practice, including the potential for conceptual distortions due to historical factors. It is argued that historical considerations need to be included as part of the use and critical assessment of basic concepts in science.

The segmental Bauplan of the rostral zone of the head in vertebrates.

Observations in a wide selection of lower vertebrate embryos have confirmed classical descriptions concerning segmentation of the early head mesoderm. The premandibular (PM) segment is seen as the most rostral representative of a continuous rostro-caudal series of condensations in the paraxial mesoderm, luminisations within which are secondary and variable in occurrence and form. The premandibular condensations are typically in continuity across the midline; the confluence, which comes to lie behind Rathke's pouch, marks the site of first mesoderm formation behind the oral membrane. The underlying consistency of pre-otic segmental pattern throughout the vertebrates is frequently obscured by superimposed variation in morphological detail between species, reflecting the dynamic nature of the morphogenetic tissue processes. Luminisation is one such morphogenetic epiphenomenon. Variations in it account for the terminal (Platt's) vesicle and "proboscis pores": such structures cannot therefore be safely used to infer evolutionary homologies. Many previous difficulties facing segmentation theory are explained as the result of failure to take account of the dynamic nature of the responsible morphogenetic events.

The fate map of the chick forelimb-bud and its bearing on hypothesized developmental control mechanisms.

Carbon particles and isotopic quail grafts were used as markers to study the salient features of the fate map of the chick forelimb between stages 20 and 27. The grafting technique confirmed the reliability of the carbon method: they both revealed striking asymmetries in which apical mesodermal tissue was progressively displaced in a proximal direction (as would be expected on the basis of growth by net apical addition of tissue) but also in a preaxial direction, while postaxial tissue became elongated in the direction of limb outgrowth. Ectoderm showed a similar preaxial-postaxial asymmetry but became displaced from initially underlying mesoderm. In marked contrast to mesoderm, distal ectoderm remained at a constant distance from the apical ectodermal ridge (or became incorporated into it), thus implying that the ectodermal sheet is anchored distally and grows by uniform stretching proximally. Within the ectoderm itself, the outer peridermal layer is displaced distally relative to the underlying epidermal basal layer. Peripheral mesoderm showed patterns of displacement which were intermediate between those of ectoderm and chondrogenic core mesoderm. It is argued that such morphogenetic phenomena are integral components of developmental mechanisms of significance in the control of pattern generation. Implications of the interpretation and use of the fate map in relation to theories of limb development, particularly those based on mechanisms defined in terms of limb axes, are reviewed.

Consequences of misrouting goldfish optic axons.

Cut optic axons regenerate into the goldfish tectum by indirect routes. To study the accuracy with which they terminate we made visuotectal maps before and immediately after cutting through the rostral tectum from its medial edge. This severed the normal pathway to medial tectum leaving intact only grossly misrouted axons. In fish mapped in this way, 3 months or more after contralateral optic nerve cuts, each initial map was essentially normal. After a tectal cut the electrical responses were usually weaker; but their receptive field positions proved to match very closely those noted previously for the same recording sites. The mean angular change was only 8.48 degrees and much of this could be accounted for by experimental errors. In fish mapped 6 months or more after attempts to cross-unite the optic tract brachia, initial maps were less regular. Some showed gross rearrangement of groups of terminals; and recognizable irregularities persisted in two fish mapped again after a further 4 or 5 months. However, maps made after tectal cuts in such fish were not noticeably less regular than the initial maps. Field position changes averaged 17.85 degrees. In both groups misrouted axons, filled with horseradish peroxidase after mapping and visualized in whole-mounts, crossed the tectum from lateral regions to reach the medial recording sites. The small field position changes in both groups confirm that axons from detectable terminals only among their retinal neighbours; nevertheless the irregular maps seen after tract cross-union lead us to expect the orderly arrangement of the normal pathway to contribute significantly to the precision of the normal map.

Evidence for an orderly arrangement of optic axons within the optic nerves of the major nonmammalian vertebrate classes.

The pathways of selected optic axons were traced in representative urodele, anuran, teleost, reptile, and avian species by filling the fibers with HRP or by tracing, at the light and electron microscopic (EM) level, the degeneration caused by focal retinal or optic nerve lesions. In all species it was shown that fibers retain retinotopic neighborhood relationships throughout their transit of the optic nerve. Additionally, in anurans, it was found that a subset of large diameter, myelinated fibers take up a random arrangement in the nerve. It is argued that retinotopic fiber organisation is a reflection of contact guidance of axons during fiber outgrowth in the embryo and that this organisation could account for the arrival of fibers in orderly arrays at central nuclei during normal embryonic development.

Some determinants of optic terminal localization and retinotopic polarity within fibre populations in the tectum of goldfish.

1. The reorganization of the retinotectal projection which results after partial ablation of tectal tissue was examined in goldfish using electrophysiological methods. 2. Regardless of the size of a unilateral ablation of caudal tectum, an orderly and virtually complete, 'compressed', visual projection re-formed on the remaining tectum after crushing the optic nerve and allowing it to regenerate. 3. If the optic nerve was left intact after ablations of caudal tectum, compressed projections were only found when the ablations were small. Large caudal ablations involving half or more of the dorsal tectum resulted in the cut fibres transposing onto the remaining tectum and forming an overlaid, 'duplicate', projection on the remaining intact projection. 4. In approximately one third of cases the duplicate projection lay in a reversed polarity along the rostrocaudal axis of the tectum. In the remaining cases the polarity of the duplicate projection was normal. 5. Transposed projections of reversed rostrocaudal polarity could be consistently obtained by ablating temporal retina and caudal tectum, leaving an intact strip of fibres terminals along the caudal edge of the tectal remnant. 6. Compression and duplication occurred in the same way if fish were maintained in constant light. 7. After ablations of lateral tectum, leaving the optic nerve intact, compression and some disorderly duplications were found. 8. Reversed projections could be induced across the mediolateral axis of dorsal tectum by denervating the medial tectum and ablating a strip of lateral tectum. 9. Projections of normal polarity were found after the optic nerve was allowed to regenerate into tecta which had previously supported reversed polarity projections.

Selection of appropriate medial branch of the optic tract by fibres of ventral retinal origin during development and in regeneration: an autoradiographic study in Xenopus.

The formation of the branches of the optic tract has been studied with the use of [3H]proline autoradiography, during development and during regeneration of the optic nerve in Xenopus with one compound ventral (VV) eye made by the embryonic fusion of two ventral eye fragments. The formation of the optic pathway was abnormal in that the lateral branch failed to develop, suggesting that fibres from a VV retina selectively entered the tectum via the medial branch during development. Three months after section of the optic nerve of a VV eye, regenerated fibres were present both in the contralateral and ipsilateral tecta. On the ipsilateral side regenerated fibres entered the tectum via the medial branch only. Retinal fibres entered the contralateral tectum through both branches in some animals and through the medial branch only in others. It is concluded that mechanical factors alone are insufficient to explain the phenomenon of selection of the appropriate medial branch by fibres of ventral retinal origin either during development or in regeneration. Some form of fibre-substrate interaction seems to be necessary; and this ability of fibres from a VV eye to take the path appropriate for ventral retina argues strongly that the VV eye is not a regulated system in terms of cell specificities.