April 8, 2008
When a hand or, more likely these days, a cell phone inadvertently smacks our cheek, the blow instantaneously triggers a flow of feedback information via the trigeminal nerve to a rounded nexus of nerve fibers called the trigeminal ganglion. There, the signal is relayed to the brain stem, merges into sensory pathways en route to the hypothalmus, and results in our reaction to wince in pain. As remarkable as the bioengineering of this process is, the developmental biology that underlies it is equally intriguing. Take the trigeminal ganglion. How do nerve-forming precursor cells self organize in the embryo in such a way that they produce an anatomically correct sensory network that forms the right connections to the central nervous system? Many of the answers are wired into the molecular circuitry of two transient embryonic cell types called neural crest cells and ectodermal placodes. They interact during embryonic development to differentiate into the nerve cells that form the trigeminal ganglion. But for a variety of technical reasons, virtually nothing is known about the molecular interplay that mediates this interaction. It’s a biological puzzle without any known pieces.
In the March issue of Nature Neuroscience, NIDCR grantees and colleagues introduce the first two pieces to the molecular puzzle. They demonstrate in animal studies that the cranial subtype of neural crest cells express the protein Slit1 on their surface while embarking on their programmed migration to the trigeminal-forming ectodermal placodes. Meanwhile, as the trigeminal placode cells follow their developmental program and ingress into adjacent embryonic tissue, they express on their surface the Robo2 protein, the known receptor for the Slit1 protein. The implication: The Robo2-Slit1 connection, like fitting a hand in a glove, mediates the needed interaction of neural crest and trigeminal placode cells during the formation of sensory ganglia. As the scientists showed, whenever they disrupted one or both of these molecular signals, the resulting sensory ganglia were structurally abnormal.