Endocrine Abstracts

Over one hundred years ago Ramon y Cajal proposed that developing axons

might be guided to their targets by diffusible chemical signals but the

first evidence that this was possible did not emerge until 1983. Ten years

later saw the first evidence for diffusible repellent signals that restrict

the territories occupied by axons and the first identified chemorepellent,

collapsin, (now known as Sema 3 A). In 1994 the prototype axonal

chemoattractant, netrin-1 was purified. It has only been more recently

shown that these and other axon-guidance cues, such as the slit proteins,

also contribute to the migratory patterns of whole neural cells rather than

just their axons. Much is now known about the receptors that mediate these

guidance cues and reflects the very rapid progress at molecular level in

the past decade. In addition to mechanisms operating through secreted

signals there are signalling mechanisms such as Eph-ephrin interactions

which operate via cell to cell contact to bring about precise positional

organisation. All of these guidance systems function against the backdrop

of the extracellular matrix which also provides permissive and inhibitory

signals which regulate the migration of cells and movement of their

axons. Permissive functioning of the extracellular matrix is largely

provided by the laminin glycoproteins and their cognate receptors, the

integrins. Inhibitory interactions result from cellular interactions with

molecules such as chondroitin sulphate proteoglycans and heparan sulphate

proteoglycans

Thus, there are diffusible and non-diffusible attractant and repellent

signals for axon-guidance and cell migration that can operate in a

'push-pull' manner to orchestrate the patterning of the nervous system.