Differential expression of cadherins has been seen in the brain, so Jessell looked to see which cadherins are made in chick spinal cord. He studied defined motor pools, each of which innervates a single limb muscle, and found 15 cadherins, 7 of which were expressed in different subsets of the motor pools. Combinations of these cadherins could easily account for the 40 pools needed to innervate the 40 muscles in one limb.
Two of the pools—EF and A—were well suited to further analysis. These two pools shared expression of three different cadherins, but only the A pool expressed the additional MN-cadherin. When Jessell eliminated this difference in cadherin profile by expressing either MN-cadherin in the EF pool or a dominant–negative version of MN-cadherin in the A pool, the cells from the two pools intermixed. The effect was pool and cadherin specific.
But pool identity probably does not start with cadherin expression, or even with a geographical code. “The pools are not organized in any clear inside-out or dorsal-ventral pattern,” says Jessell. “I think it's related to the birth date of the motor neurons.”
In this scheme, earlier-born neurons could instruct the identity of later-born neurons as they arise. The later-born neurons then migrate outwards through the older neurons, and it is here that cadherin expression may be important in keeping the two populations distinct as they slip past each other. Further subdivision of pools occurs after the initial migration, although Jessell does not yet know if cadherins are important in this second process.
Even the need for pools is a bit of a mystery. The motor neurons link to sensory neurons, which function perfectly well despite being jumbled and intermixed in various ganglia outside the spinal cord. Clustering may help the motor neurons to fire a coordinated movement signal, as the neurons in a pool are electrically coupled. Jessell plans to test this idea by globally disrupting all cadherin interactions. Existing evidence suggests that this will scramble the motor neuron pools but allow the individual cells to maintain the transcription factor mix that defines their identity. ▪