At the 19th annual meeting of the Society for Neuroscience, under way this week in Phoenix (see story on page 1), more than 150 papers will be presented on the subject of growth cones, including such aspects as process outgrowth and guid- ance mechanisms in neuronal differentiation, morphogenesis, and development.
This represents a more than three-fold increase over the number of papers on this topic delivered just five years ago (see accompanying chart). By comparison, the total number of. abstracts submitted for the society’s annual meeting increased by “only” 73% over this same period. All in all, this trend serves to indicate the emerging importance of growth cone studies.
“One reason this field has recently gotten so hot is because researchers can now see what they could only imagine before,” says Stephen Smith, a Howard Hughes investigator in the Section of Molecular Neurobiology, Yale University School of Medicine. “New technologies such as fluorescent probe compounds used in conjunction with digital light microscopy allow just about anyone to see what growth cones look like, and everyone, even those not trained in biology, find the sight fascinating.”
Growth cones—sensory tips or endings of growing neurons that guide a neuron’s axon to its proper target during embryonic and postnatal development—vary in size, shape, and behavior. When growth cones reach their targets, they become secretory presynaptic terminals, and the corresponding target cells become postsynaptic complexes. In other words, a growth cone becomes a synapse once it arrives at its “correct” position.
Electron light microscopy has allowed researchers to watch and photograph how growth cones travel to these targets. The growing nerve fibers send out filopodia, or “short processes,” which “taste” their surroundings and react either by retracting or by adhering to the cell or substrate and then moving forward. But what hasn’t yet been determined is the exact mechanism that guides growth cones to their target cells. Smith puts the question this way: “How do the synaptic partners find each other within the complex structures of the developing brain?”
Growth cones appear to follow fibers, grooves, and tracks of adhesiveness to reach their target cells. Some research indicates that they have an affinity for laminin—a substrate adhesion molecule secreted by cells in the extracellular matrix— while other investigations indicate that they move along axons that preceded them on the same path (D. Bray, P.J. Hollenbeck, Annual Review of Cell Biology, 4:43-61, 1988).
Growth cones also may follow signals on the surfaces of cells and in the extracellular environment to guide them through the nervous system. There is evidence that neuronal growth cones are attracted to their cellular targets by chemoattractant or chemotrophic molecules (“attractive cues”) that emanate from these cells. Also, repellent molecules may be working to inhibit axon extension (J. Dodd, T.M. Jessell, Science, .242:692-9, Nov. 4, 1988).
Corey S. Goodman, a Howard Hughes investigator at the University of California, Berkeley, is hop- ing to learn how growth cones navigate through the complex structures of the brain by studying the central nervous system (CNS) of Drosophila and the peripheral nervous system of the grasshopper Schistocerca americana. Goodman has pointed out that studying insects offers the neuroscientist a combination of cellular, classical genetic, and molecular genetic approaches to the study of cellular and molecular mechanisms of growth cone guidance and neuronal recognition.
“As it turns out,” Goodman tells The Scientist, “the more researchers find out about growth cones at the molecular level, the more similar they appear to be in both vertebrates and invertebrates—similar not only in terms of mechanisms but also in terms of using the very same molecules. These findings are heartening, because it means that research involving invertebrate neuronal systems can be applied directly to the study of growth cones in vertebrates. This is really exciting, since one can study the genetic aspects of nervous system development quite easily in the fruit fly.”
This topic also holds out the promise for future practical applications’ in medicine. “Understanding how growth cones develop could help doctors learn how to repair and even to prevent damage caused by trauma,” says Smith. “Researchers may someday even learn how to put a shattered nervous system back together again based on work being done today. That is, of course, still a wild-eyed dream, but in the not-so-distant future researchers will be able to imagine how this might be done.” In fact, although neurons in the CNS don’t grow back when injured, damaged neurons in the peripheral regions do regenerate, giving investigators hope that they may someday learn how to trigger regrowth in the CNS.
Goodman notes that research on diseases caused by congenital abnormalities will benefit as well from the study of growth cones by providing a foundation of knowledge about early development of the central nervous system.
Abigail is Grissom is a freelance science writer based in Philadelphia.