Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1202 Chapter 21: Development of Multicellular Organisms
axon
dynamic microtubules
lamellipodia
microtubules
filopodia
(A)
20 µm
(B)
(C)
(D)
actin
meshwork
actin
bundle
contacts an unfavorable surface, it withdraws; when it contacts a more favorable
surface, it persists longer, steering the growth cone in that direction. In this way,
the growth cone is guided by subtle variations in the properties of the surfaces
over which it moves. At the same time, it is sensitive to specific signaling molecules,
which—as we discuss next—can either encourage or hinder its advance.
A Variety of Extracellular Cues Guide
MBoC6
Axons
n22.234/22.73
to their Targets
Growth cones generally travel toward their targets along predictable routes,
according to programs stored in the memory of the particular neuron to which
they belong (Movie 21.7). In the simplest case, a growth cone can take a route that
has been pioneered by other neurites, which they follow by contact guidance. As a
result, nerve fibers in a mature animal are usually found grouped together in tight
parallel bundles (called fascicles or fiber tracts). Such crawling of growth cones
along axons is partly mediated by homophilic cell–cell adhesion molecules—
membrane glycoproteins that help a cell displaying them to stick to any other cell
that displays the same molecules. As discussed in Chapter 19, many homophilic
adhesion molecules fall into one of two main classes: they are members of either
the immunoglobulin superfamily, such as N-CAM, or the Ca 2+ -dependent cadherin
family, such as N-cadherin. Members of both families are generally present
on the surfaces of growth cones, of axons, and of various other cell types that
growth cones crawl over, including glial cells in the central nervous system and
muscle cells in the periphery of the body. Growth cones also migrate over components
of the extracellular matrix. When tested with neurons growing in a culture
dish, some of the matrix molecules, such as laminin, favor axon outgrowth, while
others, such as chondroitin sulfate proteoglycans, discourage it. But exactly how
the matrix functions to guide axons in intact animals remains to be discovered.
Growth cones are generally guided by a succession of different cues at different
stages of their journey, as summarized in Figure 21–73. Many of these cues
involve specific signaling molecules. Some of these are encountered in the extracellular
matrix, while others are attached to the plasma membrane of cells that
the growth cones touch. Another important part is played by chemotactic factors;
these are proteins secreted from cells that act as beacons at strategic points along
the path—some attracting, others repelling. The trajectory of commissural axons—
axons that cross from one side of the body to the other—provides a well-studied
example.
Commissural axons are a general feature of bilaterally symmetrical animals,
such as us, because they are required to coordinate behavior of the two sides of
the body. In the developing spinal cord of a vertebrate, for example, a large number
of neurons send their axonal growth cones ventrally toward the floor plate
(the same structure that we encountered earlier as a source of the morphogen
Sonic hedgehog—see Figure 21–69). The growth cones cross the floor plate and
then turn abruptly through a right angle to follow a longitudinal path up toward
the brain, parallel to the floor plate but never again crossing it (Figure 21–74). The
first stage of the journey depends on a concentration gradient of the signal protein
Netrin, secreted by the cells of the floor plate: the commissural growth cones sniff
their way toward its source.
Figure 21–72 Internal architecture
of a neuronal growth cone, as seen
in culture on a flat substratum. The
growth cone forms as an expansion of
the tip of the growing axon. (A) Image by
interference-contrast microscopy.
(B) Immunostaining to show microtubules
(green). (C) Immunostaining to show
actin filaments (red). (D) Diagram of the
cytoskeletal machinery. Filopodia form
and push forward by assembly of actin
filaments at the leading edge of the
growth cone. Microtubules stabilize the
directional decisions made by the actin-rich
protrusions. Filopodia adhering to the flat
substratum contract and pull the growth
cone forward. (Images by Chi-Hung Lin,
Paul Forscher Laboratory, Yale University,
New Haven, CT.)