An important process in the organization of the developing nervous system is the clustering of neurons with similar properties to form nuclei. In a new study reported in Cell, Price et al. have examined how motor neurons in the spinal cord sort themselves into 'motor pools' — collections of neurons that innervate a common muscle target. It was already known that each motor pool expresses a distinct combination of transcription factors, but here the authors turned their attention to cell-surface molecules that might enable neurons of the same motor pool to recognize one another. Their results indicate an important role for adhesion molecules of the type II cadherin family.

Price et al. cloned 15 different cadherins from the chick embryo spinal cord, and they examined their expression patterns at the lumbar level, where the motor pools have been best characterized. They found that most motor pools express more than one cadherin gene, and each expresses a different combination of type II cadherins. This pattern is achieved through two mechanisms: some genes, such as MN-cad, cad-12 and cad-8, are initially expressed in most or all motor neurons and are subsequently downregulated in certain pools, whereas others, such as T-cad, cad-6b and cad-7, are activated in a fraction of motor neurons after they have left the cell cycle. The emergence of these expression patterns coincides with the time when the neurons are beginning to segregate, making the cadherins good candidates for driving this segregation.

The authors looked at the development of two motor pools, eF and A, which differ in the expression of a single type II cadherin (A expresses MN-cad, but eF does not). They generated mosaic embryos in which MN-cad was either expressed ectopically or inactivated in a random selection of cells. Both manipulations led to increased intermingling of eF and A neurons, indicating that MN-cad is important for the segregation of neurons between these two motor pools.

They also showed that misexpression of the transcription factor Er81 causes ectopic expression of MN-cad, raising the possibility that the transcriptional profile of motor neurons translates into a cadherin 'code' on the cell surface. So, although this research is still at an early stage, the type II cadherins are already emerging as a possible link between transcription-factor expression and neuronal surface properties in motor pools.