The notochord is the defining structure of the chordates, and has essential roles in vertebrate development. It serves as a source of midline signals that pattern surrounding tissues and as a major skeletal element of the developing embryo. Genetic and embryological studies over the past decade have informed us about the development and function of the notochord. In this review, I discuss the embryonic origin, signalling roles and ultimate fate of the notochord, with an emphasis on structural aspects of notochord biology.

Structure and function of the notochord: an essential organ for chordate development.

Several models have been proposed for the generation of the rostral nervous system. Among them, Nieuwkoop's activation/transformation hypothesis and Spemann's idea of separate head and trunk/tail organizers have been particularly favoured recently. In the mouse, the finding that the visceral endoderm (VE) is required for forebrain development has been interpreted as support for the latter model. Here we argue that the chick hypoblast is equivalent to the mouse VE, based on fate, expression of molecular markers and characteristic anterior movements around the time of gastrulation. We show that the hypoblast does not fit the criteria for a head organizer because it does not induce neural tissue from naive epiblast, nor can it change the regional identity of neural tissue. However, the hypoblast does induce transient expression of the early markers Sox3 and Otx2. The spreading of the hypoblast also directs cell movements in the adjacent epiblast, such that the prospective forebrain is kept at a distance from the organizer at the tip of the primitive streak. We propose that this movement is important to protect the forebrain from the caudalizing influence of the organizer. This dual role of the hypoblast is more consistent with the Nieuwkoop model than with the notion of separate organizers, and accommodates the available data from mouse and other vertebrates.

Reconciling different models of forebrain induction and patterning: a dual role for the hypoblast.

Animal models play a crucial role in fundamental and medical research. Progress in the fields of drug discovery, regenerative medicine and cancer research among others are heavily dependent on in vivo models to validate in vitro observations, and develop new therapeutic approaches. However, conventional rodent and large animal experiments face ethical, practical and technical issues that limit their usage. The chick embryo represents an accessible and economical in vivo model, which has long been used in developmental biology, gene expression analysis and loss/gain of function experiments. It is also an established model for tissue/cell transplantation, and because of its lack of immune system in early development, the chick embryo is increasingly recognised as a model of choice for mammalian biology with new applications for stem cell and cancer research. Here, we review novel applications of the chick embryo model, and discuss future developments of this in vivo model for biomedical research.

The chick embryo: hatching a model for contemporary biomedical research

An experimental study of the independent differentiation of the isolated Hensen's node and its relation to the formation of axial and non‐axial parts in the chick embryo

An "organizer" is formally defined as a region, or group of cells in an embryo that can both induce (change the fate) and pattern (generate an organized set of structures) adjacent embryonic cells. To date, about four such regions have been demonstrated: the primary or Spemann organizer (Hensen's node in amniotes), the notochord, the zone of polarizing activity of the limb bud, and the mid-hindbrain boundary. Here we review the evidence for these and compare them with a few other regions which have been proposed to represent other organizers and we speculate on why so few such regions have been discovered.

Organizers in Development.

IT has recently proved possible to cultivate young chicken and duck embryos in vitro, using the ‘watch-glass technique’ employed at the Strangeways Laboratory for the cultivation of embryonic organs. Experiments using a somewhat similar technique were made in this laboratory two or three years ago by T. S. P. Strangeways and D. H. Strangeways, but the work was given up after a few trials and the results never published. The embryos can easily be kept alive for two or three days and differentiate nearly normally, although the rates both of differentiation and of growth are slower in vitro than in vivo. I wish here to summarise some experiments which I have recently performed on this material: full reports will be published in the near future.

C. H. Waddington

Papers

Developmental Mechanics of Chicken and Duck Embryos