Thomas Jessell and his associate Shanthini Sockanathan discovered that a motor neuron’s birth date plays a role in determining that neuron’s fate.
Photo: Chris Denney

Birthdays Are Important

Studies of motor neuron development also indicated that there must be factors in addition to sonic hedgehog that play an influential role in determining motor neuron fate. "It turns out that a motor neuron’s birth date is another critical determinant of fate," Jessell says.

Jessell and his associate Shanthini Sockanathan discovered that early-born motor neurons of the lateral motor column—the neurons that project to the limb muscles—secrete retinoic acid, an active metabolite of vitamin A. Late-born lateral motor column neurons must migrate past early-born neurons to arrive at their final destination in the CNS. The two populations—early-born and late-born—wire the ventral and dorsal limb muscles respectively. In the August 21, 1998, issue of Cell, Jessell and Sockanathan reported that the retinoic acid to which these migrating late-born motor neurons are exposed establishes their fate.

So, while Jessell and his colleagues feel that they are slowly gaining a better understanding of how motor neurons mature, they know they have only half the picture: They still know comparatively little about how the sensory neuron part of that circuit is established. "When you move a limb," Jessell explains, "it’s not sufficient to just contract or flex specific muscles. You also require sensory feedback to tell the central nervous system how the muscles contracted."

Jessell is now investigating how this feedback loop is established, and in the process, he may be coming closer to understanding the mature nervous system, the structure of which so intimidated him as a graduate student. "We’ve known that the nervous system has to coordinate the extension and contraction of a variety of muscles just to take a simple step, but nobody has provided any molecular explanation of this supposedly simple neural function. We may soon be at the point where we can begin to examine the specificity of neural connections themselves," he says. "At this point perhaps it will be possible to gain some insight not only into the assembly of circuits but also the principles by which they are organized in the mature nervous system." 

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