The Questions of Developmental Biology

16. Some proteins are generally permissive to neuron adhesion and provide substrates on which
axons can migrate. Other substances prohibit migration.
17. Some growth cones recognize molecules which are present in very specific areas and
therefore will be guided by these molecules to their respective targets.
18. Some neurons are "kept in line" by repulsive molecules. If they wander off the path to their
target, these molecules bring them back. Some molecules, such as the semaphorins, are
selectively repulsive to a particular set of neurons.
19. Some neurons sense gradients of a protein and are brought to their target by following these
gradients. The netrins may work in this fashion.
20. Target selection can be brought about by neurotrophins, proteins that are made by the target
tissue that stimulate the particular set of axons that can innervate it. In some cases, the target
makes only enough of these factors to support a single axon.
21. Address selection is activity-dependent. An active neuron can suppress synapse formation by
other neurons on the same target.
22. Retinal ganglial axons in frogs and chick send axons that bind to specific regions of the optic
tectum. This process is mediated by numerous interactions, and the target selection appears to be
mediated through ephrins.
23. In some instances, fetal neurons can integrate into adult brains and re-establish damaged
synapses.
24. Some behaviors appear to be innate ("hard-wired") while others are learned. Experience can
strengthen certain neural connections.
*The growth cones of pioneer neurons migrate to their target tissue while embryonic distances are still short and the
intervening embryonic tissue is still relatively uncomplicated. Later in development, other neurons bind to the pioneer
neuron and thereby enter the target tissue. Klose and Bentley (1989) have shown that in some cases, the pioneer
neurons die after the other neurons reach their destination. Yet, if those pioneer neurons were prevented from
differentiating, the other axons would not have reached their target tissue.
The binding of a soluble factor to the extracellular matrix makes for an interesting ambiguity between chemotaxis,
haptotaxis, and labeled pathways. Nature doesn't necessarily conform to the categories we create.
In recent years, researchers have discovered dozens of mutations in zebrafish that affect the migration of the retinal
ganglion axons to the tectum or the specificity of the retinotectal connections. These mutants are only now being
analyzed, but they promise to provide major insights into the mechanisms by which our sensory input enters the brain.
The December 1996 (Volume 123) issue of Development contains several articles mapping the genes involved in the
migration of the axon from the retina to the optic cortex. Over 30 mutant genes have been found that affect either the
ability of zebrafish retinal ganglion axons to find the optic tectum or the ability of the axons to find their appropriate
connections within the tectum (Karlstrom et al. 1997).