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

NEURAL DEVELOPMENT
1203
extracellular matrix adhesion
growing axon
guidance by pioneer neuron
cell surface adhesion
chemoattraction
Figure 21–73 Mechanisms of growthcone
guidance. Growth cones use a
variety of extracellular cues to navigate
to distant targets. They can adhere to
the extracellular matrix or to the surfaces
of other cells, or they can be repelled by
them; they can crawl, for example, by
homophilic adhesion along the axons of
pioneer neurons; and they can be attracted
or repelled by soluble guidance signals.
(After E. Kandel et al., Principles of Neural
Science, 5th ed., New York: McGraw Hill
Medical, 2012.)
contact inhibition
chemorepulsion
target neuron
If commissural growth cones are attracted to the floor plate, why do they cross
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it and emerge on the other side, instead of staying in the attractive territory? And
having crossed it, why do they never cross back again? The answers lie in a change
in the responsiveness of the growth cones during their journey. As the growth
cones cross the midline, they lose sensitivity to Netrin and become sensitive
instead to a signal protein called Slit (see Figure 21–74). Slit is also produced by
the floor plate, but it has the opposite effect to that of Netrin: it repels the growth
roof plate
DORSAL
commissural
neuron approaching
midline
floor plate on
ventral midline
commissural
neuron
attractant
(Netrin)
TOWARD BRAIN
(B)
growth cone expressing receptors
for Netrin and Slit, plus Robo3.1
that inhibits Slit receptors
growth cone expressing
receptors for Slit and
Netrin
commissural
axon
(A)
midline
floor plate
VENTRAL
(C)
repellent
(Slit)
TO BRAIN
Figure 21–74 The guidance of commissural axons. (A) The pathway taken by commissural axons in the embryonic spinal cord of a vertebrate.
(B) Attraction to the midline. The growth cone is first attracted to the floor plate by Netrin, which is secreted by the floor-plate cells and acts on the
receptor DCC in the axonal membrane. (C) Repulsion from the midline after crossing it. As the growth cone crosses the floor plate, Slit comes into
play: it binds to its receptors Robo1 and Robo2 and acts as a repellent to keep the growth cone from re-entering the floor plate. In addition, it blocks
responsiveness to the attractant Netrin. Before crossing the midline, the commissural neurons express Robo3.1, an alternative splice form of Robo3
that is related to Robo proteins but blocks Slit signaling. As neurites cross the midline, Robo3.1 is lost and growth cones become responsive to Slit
and are repelled from the midline.
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