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Netrin-1 expression pattern in the floorplate
In vitro assay of floorplate & Netrin-1
Ventral hindbrain
Floor plate
FIGURE 5.36 Trochlear motor neurons are repelled by netrin. A.
Trochlear motor neurons arise in the ventral neural tube at the mid-
brain/hindbrain region. They grow away from the ventral midline
to decussate and leave the brain dorsally. B. Trochlear neurons in a
collagen gel explant culture grow away from the floorplate, and C.
from COS cells expressing Netrin. (After Colamarino and Tessier-
Lavigne, 1995)
COS cells
FIGURE 5.35 Midline crossing mutants in Drosophila. A. In
normal flies, many neurons cross the midline once in a commissure
and then travel in longitudinal fascicles on the other side. B. In com-
missureless mutants, the axons do not cross but travel in longitudinal
tracts on the same side. C. In roundabout mutants, the longitudinal
tracts do not form properly because the axons keep crossing back
and forth. (After Seeger et al., 1993)
6 at the ventral midline, are made to misexpress
Unc-5, these axons now grow dorsally instead, again
depending on the normal expression of Unc-6 to do so.
Unc-5, like Unc-40, codes for a transmembrane protein,
possibly another Unc-6 receptor, but is involved in
chemorepulsion rather than chemoattraction.
This means that Netrins can act as chemorepulsive
agents for neurons that express Unc-5 type receptors
and chemoattractive factors for neurons that express
Unc-40 or DCC-type Netrin receptors. That Netrin
can act as a long-range chemorepulsive factor in verte-
brates has been demonstrated in trochlear motor
neurons whose axons grow dorsally away from the
ventral midline (Colamarino and Tessier-Lavigne,
1995) (Figure 5.36). In collagen gels, these axons grow
away from explanted floorplate tissues or from cells
transfected with a Netrin-1 expressing gene. The switch
from attraction versus repulsion to Netrin can be medi-
ated by the expression of a different receptor such as
diate target. These axons must not get stuck where the
Netrin concentration is highest, but should move on
and take the next portion of their journey. One way to
do this is to make an attractant either unattractive or
even downright repulsive. Netrin (or Unc-6) is attrac-
tive for axons that express DCC (or Unc-40). Mutants
in DCC (or Unc-40) disrupt the migration of axons
toward Netrin (or Unc-6). The unc-5 mutant has the
opposite phenotype. It disrupts dorsal migration
(Culotti, 1994), but the unc-5 phenotype is dependent
on wild-type unc-6 function. Interestingly, when
neurons whose axons normally grow toward the Unc-
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