The notochord

Abstract

What is the notochord? The notochord is the defining structure of the phylum Chordata, which includes all vertebrates. In its ‘mature’ state the notochord is a rod of large cells constrained by a thick extracellular sheath and positioned between the developing spinal cord and gut. Turgor pressure generated by notochord cells exerted against the sheath gives the notochord stiffness, imparting the mechanical properties required for one of its main functions as the central axial skeletal element of the developing embryo. What does it do? The notochord exists transiently during the life of most vertebrates. During its short life, however, the notochord plays another critical role for developing embryos. It produces a variety of secreted growth factors, such as Sonic hedgehog, which instruct surrounding tissues to acquire particular differentiated fates. A number of embryological experiments, for example, tell us that, without notochord-derived signals, motorneurons in the spinal cord would not form, the pancreas insulin-producing cell would not differentiate and the body muscles would not be produced properly. Without the axial skeletal support of the notochord, many lower vertebrate larvae, such as fish fry and tadpoles, become severely shortened and cannot swim or feed properly. Thus many of the mutations affecting zebrafish notochord development are named after the seven dwarves. Where does it come from? One of the truly classic experiments of embryology is the ‘organiser’ experiment of Spemann and Mangold. In the original experiment, a piece of the dorsal side of a newt embryo was transferred from one species (with dark pigment) to the ventral side of an equivalently staged embryo of another, lightly pigmented newt species. Amazingly, the resulting embryos were conjoined twins, with one original body axis and a second body axis induced by the transplanted dorsal tissue. For the notochord enthusiast, the most astounding thing about this is that the majority of tissue derived from the graft is notochord, while the induced second axis is derived mostly from the host. The same activity has been identified for other vertebrate phyla, with an equivalent piece of dorsal notochord progenitor tissue able to induce the formation of a second axis. Figure 1 shows an example of such an experiment with zebrafish. Thus, well before acquiring the morphological characteristics of a notochord the progenitor tissue possesses the remarkable ability to organise embryogenesis. From an evolutionary point of view recent studies of a group of lower chordates, called ascidians, are beginning to give us insight into some of the genes important for notochord formation. Ascidians, also known as tunicates or sea-squirts, are most familiar in their sessile adult stages, but as free-swimming larvae ascidians possess a notochord that serves as the main skeletal element. In one study a gene called Manx, which is important for notochord formation, was identified by comparing gene expression in two related species of ascidian, one possessing a normally differentiated notochord with another tail-less species. Where does it go? By the time the notochord is mature it expresses a constellation of genes that is essentially identical to that of developing cartilage. This is consistent with the mechanical role of the notochord. Indeed, in birds, most fish and mammals the notochord becomes segmented and in regions of vertebrae expresses type X collagen and is replaced by bone while in the intervertebral regions notochord cells contribute to the centre of the discs. Where can I find out more?