Neuronal connections form during embryonic development
when neurons send out axons, tipped at their leading edge by
the growth cone, which migrate through the embryonic
environment to their synaptic targets. Studies of developing
axonal projections have revealed that axons extend to the
vicinity of their appropriate target regions in a highly
stereotyped and directed manner by detecting a variety of
attractive and repulsive molecular guidance cues presented by
cells in the environment (Dickson, 2002; Tessier-Lavigne and
In the 1990s, genetic, biochemical and molecular
approaches together identified four major conserved families
of guidance cues with prominent developmental effects: the
Netrins, Slits, Semaphorins and Ephrins (Dickson, 2002;
Tessier-Lavigne and Goodman, 1996). Netrins, Slits and some
Semaphorins are secreted molecules that associate with cells
or the extracellular matrix, whereas Ephrins and other
Semaphorins are anchored to the cell surface. Netrins can act
as attractants or repellents; Slits, Semaphorins and Ephrins act
primarily as repellents but can be attractive in some contexts.
For each of these sets of cues, one or more families of
transmembrane receptors have been identified: DCC and UNC-
5 receptors for Netrins, Roundabout (Robo) receptors for Slits,
Neuropilin and Plexin receptors for Semaphorins, and Eph
receptors for Ephrins. In addition to these ‘classic’ axon
guidance molecules, some growth factors, including
Neurotrophins and Scatter Factor/Hepatocyte Growth Factor
(SF/HGF), have been implicated in axon guidance (Ebens et
al., 1996; O’Connor and Tessier-Lavigne, 1999; Tucker et al.,
Although the identification of these major guidance cues has
increased our understanding of how the nervous system is
wired, many guidance events observed during development do
not appear to be accounted for by these molecules. Moreover,
the number of guidance cues and receptors identified seem
small relative to the immense complexity of nervous system
wiring; thus, additional guidance cues and receptors probably
remain to be discovered. Remarkably, over the last few years,
members from three other families of secreted signaling
molecules have been shown to act as guidance cues: the
Wingless/Wnt, Hedgehog (Hh) and Decapentaplegic/Bone
(Dpp/BMP/TGFβ) families. In addition to their axon guidance
properties, these molecules share a common characteristic of
having been previously identified as morphogens controlling
cell fate and tissue patterning. This discovery has facilitated the
study of an entirely new set of axon guidance cues and changed
our current notions about morphogenic and axon guidance
molecules. Additionally, it suggests that these proteins can be
thought of more generally as providing graded positional
information, which can be interpreted by responding cells as
either a cell-fate specification signal or one for axonal
Here, we focus on the emerging evidence that these three
morphogen families are reused later in development to guide
axons, and compare the similarities and differences in how they
provide positional information that can be interpreted for
axon guidance versus cell fate specification. Additionally, we
also briefly discuss the increasingly appreciated role for
morphogens in cell migration (Box 1).
Morphogens, cell fate specification and tissue
Morphogens are signaling molecules produced in a restricted
region of a tissue that provide positional information by
During embryonic development, morphogens act as graded
positional cues to dictate cell fate specification and tissue
patterning. Recent findings indicate that morphogen
gradients also serve to guide axonal pathfinding during
development of the nervous system. These findings
challenge our previous notions about morphogens and axon
guidance molecules, and suggest that these proteins, rather
than having sharply divergent functions, act more globally
to provide graded positional information that can be
interpreted by responding cells either to specify cell fate or
to direct axonal pathfinding. This review presents the roles
identified for members of three prominent morphogen
families – the Hedgehog, Wnt and TGFβ/BMP families –
in axon guidance, and discusses potential implications for
the molecular mechanisms underlying their guidance
Novel brain wiring functions for classical morphogens: a role as
graded positional cues in axon guidance
Frédéric Charron1,* and Marc Tessier-Lavigne1,2,†
1Department of Biological Sciences, Stanford University, 371 Serra Mall, Stanford, California 94305, USA
2Genentech Incorporated, 1 DNA Way, South San Francisco, California 94080, USA
*Present address: Molecular Biology of Neural Development, Institut de Recherches Cliniques de Montréal (IRCM), 110 Pine Ave West, Montreal, Quebec H2W 1R7,
†Author for correspondence (e-mail: email@example.com)
Development 132, 2251-2262
Published by The Company of Biologists 2005
diffusing from their source to form a long-range concentration
gradient. A cell’s program of differentiation in response to a
morphogen is dictated by its position within the gradient and
thus on its distance from the morphogen source. Two criteria
determine whether a secreted signaling protein acts as a
morphogen: it must have a concentration-dependent effect on
its target cells and it must exert a direct action at a distance.
To date, only three protein families have members that fulfill
these criteria: the Wingless/Wnt, Hh and Dpp/BMP/TGFβ
families (Teleman et al., 2001). Although there is abundant
evidence for concentration-dependent activity of signaling
proteins during development (reviewed by Gurdon et al.,
1998), evidence for direct action at a distance has only been
provided recently in some vertebrate systems (Chen and
Schier, 2001; Briscoe et al., 2001). In the following section, we
summarize briefly some of the biological processes that involve
members from each morphogen family, with a special
emphasis on vertebrate neural tube development, which
provides a convenient system in which to compare and contrast
roles of classic guidance molecules and morphogens in axon
In vertebrate embryos, one of the first steps in nervous
system development is the specification of the diverse neural
cell fates. Members of each of the three morphogen families
are expressed in the developing neural tube and are implicated
in its patterning, as summarized below.
The Hedgehog family
Hedgehog proteins are found in insects and vertebrates, but not
nematodes. There is a single Hedgehog gene in flies, and three
in mammals: Sonic hedgehog (Shh), Indian hedgehog (Ihh)
and Desert hedgehog (Dhh). Shh is secreted by the notochord
and by floor-plate cells at the ventral midline of the neural tube,
and functions as a graded signal for the generation of distinct
classes of ventral neurons along the dorsoventral (DV) axis of
the neural tube (Fig. 1A) (reviewed by Jessell, 2000; Ingham
and McMahon, 2001; Marti and Bovolenta, 2002). In
agreement with its role as a morphogen, Shh is able to induce
a range of ventral spinal cord cell fates in a concentration-
dependent manner (Roelink et al., 1995) and has been shown
to exert a direct action at a distance to specify neural tube cell
fate (Briscoe et al., 2001).
Much evidence indicates that these cell-fate-specification
and tissue-patterning activities of Hhs are mediated by
members of the Ci/Gli transcription factor family, but the
signaling mechanisms that lead to the activation of these
transcription factors are not fully elucidated (Ingham and
McMahon, 2001). Genetic and biochemical experiments have
shown that Hhs activate signaling by binding to their receptor
Patched (Ptc), which leads to the relief of Ptc-mediated
inhibition of Smoothened (Smo), also a transmembrane
protein, which can then activate downstream signaling (Fig.
2A). Smo associates directly with a Ci-containing complex,
which contains the atypical kinesin Costal 2 (Cos2) and the
protein kinase Fused (Fu) (Lum and Beachy, 2004). This
complex constitutively suppresses pathway activity. Activation
of Hh signaling reverses this regulatory effect and allows Ci to
activate transcription of Hh target genes, thus specifying cell
The Decapentaplegic/Bone Morphogenic
Protein/Transforming Growth Factor-β family
The roof plate at the dorsal midline of the neural tube is the
major source of inductive signals controlling the generation of
dorsal cell types (Lee and Jessell, 1999). Around the time when
dorsal neurons are generated, the roof plate expresses many
members of the Dpp/BMP/TGFβ family, and some of them are
required for the normal specification of dorsal neurons (Fig.
1A) (Lee et al., 1998). Whether they function specifically as
morphogens in this system remains to be determined (Jessell,
Members of the Dpp/BMP/TGFβ family regulate cell fate
by inducing the dimerization of type I and type II TGFβ
receptors, resulting in phosphorylation and activation of the
intracellular kinase domain of the type I receptor (Fig. 2B).
Targets of the type I receptor are the receptor-regulated Smads
(R-Smads) which, upon phosphorylation, associate with co-
Smads and translocate to the nucleus where they activate
The Wingless/Wnt family
Roof-plate cells also express several members of the Wnt
family (reviewed by Lee and Jessell, 1999). Although Wnt1
Development 132 (10)
Box 1. Morphogens and cell migration
In addition to their role in cell fate specification and axon
guidance, a role for morphogens in cell migration is also
becoming increasingly appreciated. In Drosophila, Hh has been
proposed to serve as an attractive cue to guide germ cell
migration through the embryo to form the primitive gonad
(Deshpande et al., 2001). In vertebrates, a negative effect of Shh
on cell migration has been described: the addition of Shh to
neural tube explants has been shown to inhibit neural crest cell
migration in vitro (Jarov et al., 2003; Testaz et al., 2001).
Although the negative effect of Shh on neural crest cells was
independent of the canonical Ptc/Smo signaling pathway, and
was apparently due to decreased integrin-mediated cell adhesion,
the positive effect of Hh on germ cells involved the canonical
Ptc, Smo and Fu signaling components.
Several TGFβ family members, including BMP7, have been
shown to elicit chemotaxis by peripheral blood monocytes and
polymorphonuclear leukocytes (Cunningham et al., 1992;
Postlethwaite et al., 1994). Although the cytoskeletal mediators
of BMPs in chemotaxis are not known, it was found that LIM
kinase, a key regulator of actin dynamics, directly interacts with
the type II BMP receptor and is activated by BMP stimulation,
suggesting a direct link between BMPs and the cytoskeleton
(Foletta et al., 2003).
In Drosophila, Wnt4 is required for cell movement during
ovarian morphogenesis (Cohen et al., 2002). However, these data
are inconsistent with a role for Wnt4 in providing a polarizing
cue; rather they indicate that Wnt4 promotes the motility of
apical cells through the regulation of focal adhesions. As this
effect requires Fz2, Dsh and PKC, the Wnt4 cell motility
pathway identified appears to be distinct from the canonical Wnt
pathway and the PCP pathway. Wnt signaling has also been
implicated in the control of cell movement in vertebrates (Strutt,
2003), but the mechanism through which Wnt proteins influence
motility in these experiments is unclear.
Together, these studies suggest that morphogens might
function widely in the control of cell motility and axon guidance,
a finding reminiscent of the growing role that classical axon
guidance molecules play in cell migration (Hinck, 2004).
in the responsive neuron results in similar guidance deficits;
and (3) evidence that growth cones of responsive axons can
respond directly to the morphogen – which may most
frequently be obtained in vitro in growth cone collapse or
turning assays. It can be expected that the level of proof that
is obtained will increase over time as the signaling pathways
linking the morphogens to the cytoskeleton for growth cone
turning are elucidated. These findings should provide entry
points with which to interfere selectively with the guidance
effects of the morphogens in the responsive neurons, without
altering their transcriptional effects either in those neurons or
in the environment. Nonetheless, the collective weight of the
experiments summarized above, many of which attempted and
succeeded, at least partly, in distinguishing between direct and
indirect effects of the morphogens, already provide strong
evidence that morphogens have widespread roles in axon
guidance, no doubt with more to come.
We thank Christelle Sabatier and Avraham Yaron for critical
reading of the manuscript, and members of the Tessier-Lavigne
Laboratory for helpful discussions. F.C. is an Arnold and Mabel
Beckman Foundation Senior Research Fellow. Research carried out
in the Tessier-Lavigne Laboratory was supported by the Howard
Hughes Medical Institute.
Augsburger, A., Schuchardt, A., Hoskins, S., Dodd, J. and Butler, S.
(1999). BMPs as mediators of roof plate repulsion of commissural neurons.
Neuron 24, 127-141.
Bonkowsky, J. L., Yoshikawa, S., O’Keefe, D. D., Scully, A. L. and Thomas,
J. B. (1999). Axon routing across the midline controlled by the Drosophila
Derailed receptor. Nature 402, 540-544.
Bourikas, D., Pekarik, V., Baeriswyl, T., Grunditz, A., Sadhu, R., Nardo,
M. and Stoeckli, E. T. (2005). Sonic hedgehog guides commissural axons
along the longitudinal axis of the spinal cord. Nat. Neurosci. 8, 297-304.
Briscoe, J., Chen, Y., Jessell, T. M. and Struhl, G. (2001). A hedgehog-
insensitive form of patched provides evidence for direct long-range
morphogen activity of sonic hedgehog in the neural tube. Mol. Cell 7, 1279-
Butler, S. J. and Dodd, J. (2003). A role for BMP heterodimers in roof plate-
mediated repulsion of commissural axons. Neuron 38, 389-401.
Callahan, C. A., Muralidhar, M. G., Lundgren, S. E., Scully, A. L. and
Thomas, J. B. (1995). Control of neuronal pathway selection by a
Drosophila receptor protein-tyrosine kinase family member. Nature 376,
Charron, F., Stein, E., Jeong, J., McMahon, A. P. and Tessier-Lavigne, M.
(2003). The morphogen sonic hedgehog is an axonal chemoattractant that
collaborates with netrin-1 in midline axon guidance. Cell 113, 11-23.
Chen, Y. and Schier, A. F. (2001). The zebrafish Nodal signal Squint functions
as a morphogen. Nature 411, 607-610.
Choi, S. E., Choi, E. Y., Kim, P. H. and Kim, J. H. (1999). Involvement of
protein kinase C and rho GTPase in the nuclear signalling pathway by
transforming growth factor-beta1 in rat-2 fibroblast cells. Cell. Signal. 11,
Cohen, E. D., Mariol, M. C., Wallace, R. M., Weyers, J., Kamberov, Y. G.,
Pradel, J. and Wilder, E. L. (2002). DWnt4 regulates cell movement and
focal adhesion kinase during Drosophila ovarian morphogenesis. Dev. Cell
Colamarino, S. A. and Tessier-Lavigne, M. (1995). The role of the floor plate
in axon guidance. Annu. Rev. Neurosci. 18, 497-529.
Colavita, A. and Culotti, J. G. (1998). Suppressors of ectopic UNC-5 growth
cone steering identify eight genes involved in axon guidance in
Caenorhabditis elegans. Dev. Biol. 194, 72-85.
Colavita, A., Krishna, S., Zheng, H., Padgett, R. W. and Culotti, J. G.
(1998). Pioneer axon guidance by UNC-129, a C. elegans TGF-beta. Science
Cunningham, N. S., Paralkar, V. and Reddi, A. H. (1992). Osteogenin and
recombinant bone morphogenetic protein 2B are chemotactic for human
monocytes and stimulate transforming growth factor beta 1 mRNA
expression. Proc. Natl. Acad. Sci. USA 89, 11740-11744.
Deshpande, G., Swanhart, L., Chiang, P. and Schedl, P. (2001). Hedgehog
signaling in germ cell migration. Cell 106, 759-769.
Dickson, B. J. (2002). Molecular mechanisms of axon guidance. Science 298,
Ebens, A., Brose, K., Leonardo, E. D., Hanson, M. G., Jr, Bladt, F.,
Birchmeier, C., Barres, B. A. and Tessier-Lavigne, M. (1996). Hepatocyte
growth factor/scatter factor is an axonal chemoattractant and a neurotrophic
factor for spinal motor neurons. Neuron 17, 1157-1172.
Fazeli, A., Dickinson, S. L., Hermiston, M. L., Tighe, R. V., Steen, R. G.,
Small, C. G., Stoeckli, E. T., Keino-Masu, K., Masu, M., Rayburn, H.
et al. (1997). Phenotype of mice lacking functional Deleted in colorectal
cancer (Dcc) gene. Nature 386, 796-804.
Foletta, V. C., Lim, M. A., Soosairajah, J., Kelly, A. P., Stanley, E. G.,
Shannon, M., He, W., Das, S., Massague, J., Bernard, O. et al. (2003).
Direct signaling by the BMP type II receptor via the cytoskeletal regulator
LIMK1. J. Cell Biol. 162, 1089-1098.
Gurdon, J. B., Dyson, S. and St Johnston, D. (1998). Cells’ perception of
position in a concentration gradient. Cell 95, 159-162.
Hall, A. C., Lucas, F. R. and Salinas, P. C. (2000). Axonal remodeling and
synaptic differentiation in the cerebellum is regulated by WNT-7a signaling.
Cell 100, 525-535.
Halstead, J., Kemp, K. and Ignotz, R. A. (1995). Evidence for involvement
of phosphatidylcholine-phospholipase C and protein kinase C in
transforming growth factor-beta signaling. J. Biol. Chem. 270, 13600-13603.
Hamelin, M., Zhou, Y., Su, M. W., Scott, I. M. and Culotti, J. G. (1993).
Expression of the UNC-5 guidance receptor in the touch neurons of C.
elegans steers their axons dorsally. Nature 364, 327-330.
He, X., Semenov, M., Tamai, K. and Zeng, X. (2004). LDL receptor-related
proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way.
Development 131, 1663-1677.
Hedgecock, E. M., Culotti, J. G. and Hall, D. H. (1990). The unc-5, unc-6,
and unc-40 genes guide circumferential migrations of pioneer axons and
mesodermal cells on the epidermis in C. elegans. Neuron 4, 61-85.
Hinck, L. (2004). The versatile roles of ‘axon guidance’ cues in tissue
morphogenesis. Dev. Cell 7, 783-793.
Hong, K., Hinck, L., Nishiyama, M., Poo, M. M., Tessier-Lavigne, M. and
Stein, E. (1999). A ligand-gated association between cytoplasmic domains
of UNC5 and DCC family receptors converts netrin-induced growth cone
attraction to repulsion. Cell 97, 927-941.
Hopker, V. H., Shewan, D., Tessier-Lavigne, M., Poo, M. and Holt, C.
(1999). Growth-cone attraction to netrin-1 is converted to repulsion by
laminin-1. Nature 401, 69-73.
Ingham, P. W. and McMahon, A. P. (2001). Hedgehog signaling in animal
development: paradigms and principles. Genes Dev. 15, 3059-3087.
Jarov, A., Williams, K. P., Ling, L. E., Koteliansky, V. E., Duband, J. L.
and Fournier-Thibault, C. (2003). A dual role for Sonic hedgehog in
regulating adhesion and differentiation of neuroepithelial cells. Dev. Biol.
Jessell, T. M. (2000). Neuronal specification in the spinal cord: inductive
signals and transcriptional codes. Nat. Rev. Genet. 1, 20-29.
Kennedy, T. E., Serafini, T., de la Torre, J. R. and Tessier-Lavigne, M.
(1994). Netrins are diffusible chemotropic factors for commissural axons in
the embryonic spinal cord. Cell 78, 425-435.
Kidd, T., Brose, K., Mitchell, K. J., Fetter, R. D., Tessier-Lavigne, M.,
Goodman, C. S. and Tear, G. (1998). Roundabout controls axon crossing
of the CNS midline and defines a novel subfamily of evolutionarily
conserved guidance receptors. Cell 92, 205-215.
Kuhl, M., Sheldahl, L. C., Park, M., Miller, J. R. and Moon, R. T. (2000).
The Wnt/Ca2+pathway: a new vertebrate Wnt signaling pathway takes
shape. Trends Genet 16, 279-283.
Lee, K. J. and Jessell, T. M. (1999). The specification of dorsal cell fates in
the vertebrate central nervous system. Annu. Rev. Neurosci. 22, 261-294.
Lee, K. J., Mendelsohn, M. and Jessell, T. M. (1998). Neuronal patterning
by BMPs: a requirement for GDF7 in the generation of a discrete class of
commissural interneurons in the mouse spinal cord. Genes Dev. 12, 3394-
Lee, Y. S. and Chuong, C. M. (1997). Activation of protein kinase A is a
pivotal step involved in both BMP-2- and cyclic AMP-induced
chondrogenesis. J. Cell Physiol. 170, 153-165.
Lu, X., Borchers, A. G., Jolicoeur, C., Rayburn, H., Baker, J. C. and
Tessier-Lavigne, M. (2004). PTK7/CCK-4 is a novel regulator of planar
cell polarity in vertebrates. Nature 430, 93-98.
Lum, L. and Beachy, P. A. (2004). The Hedgehog response network: sensors,
switches, and routers. Science 304, 1755-1759.
Lyuksyutova, A. I., Lu, C. C., Milanesio, N., King, L. A., Guo, N., Wang,
Y., Nathans, J., Tessier-Lavigne, M. and Zou, Y. (2003). Anterior-
posterior guidance of commissural axons by Wnt-frizzled signaling. Science
Marti, E. and Bovolenta, P. (2002). Sonic hedgehog in CNS development:
one signal, multiple outputs. Trends Neurosci. 25, 89-96.
Muroyama, Y., Fujihara, M., Ikeya, M., Kondoh, H. and Takada, S.
(2002). Wnt signaling plays an essential role in neuronal specification of the
dorsal spinal cord. Genes Dev. 16, 548-553.
Nash, B., Colavita, A., Zheng, H., Roy, P. J. and Culotti, J. G. (2000). The
forkhead transcription factor UNC-130 is required for the graded spatial
expression of the UNC-129 TGF-beta guidance factor in C. elegans. Genes
Dev. 14, 2486-2500.
Nelson, W. J. and Nusse, R. (2004). Convergence of Wnt, beta-catenin, and
cadherin pathways. Science 303, 1483-1487.
O’Connor, R. and Tessier-Lavigne, M. (1999). Identification of maxillary
factor, a maxillary process-derived chemoattractant for developing
trigeminal sensory axons. Neuron 24, 165-178.
Patthy, L. (2000). The WIF module. Trends Biochem. Sci. 25, 12-13.
Placzek, M., Tessier-Lavigne, M., Jessell, T. and Dodd, J. (1990).
Orientation of commissural axons in vitro in response to a floor plate-
derived chemoattractant. Development 110, 19-30.
Postlethwaite, A. E., Raghow, R., Stricklin, G., Ballou, L. and Sampath,
T. K. (1994). Osteogenic protein-1, a bone morphogenic protein member of
the TGF-beta superfamily, shares chemotactic but not fibrogenic properties
with TGF-beta. J. Cell. Physiol. 161, 562-570.
Roelink, H., Porter, J. A., Chiang, C., Tanabe, Y., Chang, D. T., Beachy,
P. A. and Jessell, T. M. (1995). Floor plate and motor neuron induction by
different concentrations of the amino-terminal cleavage product of sonic
hedgehog autoproteolysis. Cell 81, 445-455.
Sabatier, C., Plump, A. S., Le, M., Brose, K., Tamada, A., Murakami, F.,
Lee, E. Y. and Tessier-Lavigne, M. (2004). The divergent Robo family
protein rig-1/Robo3 is a negative regulator of slit responsiveness required
for midline crossing by commissural axons. Cell 117, 157-169.
Serafini, T., Kennedy, T. E., Galko, M. J., Mirzayan, C., Jessell, T. M. and
Tessier-Lavigne, M. (1994). The netrins define a family of axon outgrowth-
promoting proteins homologous to C. elegans UNC-6. Cell 78, 409-424.
Serafini, T., Colamarino, S. A., Leonardo, E. D., Wang, H., Beddington,
R., Skarnes, W. C. and Tessier-Lavigne, M. (1996). Netrin-1 is required
for commissural axon guidance in the developing vertebrate nervous system.
Cell 87, 1001-1014.
Song, H. J. and Poo, M. M. (1999). Signal transduction underlying growth
cone guidance by diffusible factors. Curr. Opin. Neurobiol. 9, 355-363.
Song, H. J., Ming, G. L. and Poo, M. M. (1997). cAMP-induced switching
in turning direction of nerve growth cones. Nature 388, 275-279.
Song, H., Ming, G., He, Z., Lehmann, M., McKerracher, L., Tessier-
Lavigne, M. and Poo, M. (1998). Conversion of neuronal growth cone
responses from repulsion to attraction by cyclic nucleotides. Science 281,
Stein, E. and Tessier-Lavigne, M. (2001). Hierarchical organization of
guidance receptors: silencing of netrin attraction by slit through a
Robo/DCC receptor complex. Science 291, 1928-1938.
Strutt, D. (2003). Frizzled signalling and cell polarisation in Drosophila and
vertebrates. Development 130, 4501-4513.
Teleman, A. A., Strigini, M. and Cohen, S. M. (2001). Shaping morphogen
gradients. Cell 105, 559-562.
Tessier-Lavigne, M. and Goodman, C. S. (1996). The molecular biology of
axon guidance. Science 274, 1123-1133.
Tessier-Lavigne, M., Placzek, M., Lumsden, A. G., Dodd, J. and Jessell, T.
M. (1988). Chemotropic guidance of developing axons in the mammalian
central nervous system. Nature 336, 775-778.
Testaz, S., Jarov, A., Williams, K. P., Ling, L. E., Koteliansky, V. E.,
Fournier-Thibault, C. and Duband, J. L. (2001). Sonic hedgehog restricts
adhesion and migration of neural crest cells independently of the Patched-
Smoothened-Gli signaling pathway. Proc. Natl. Acad. Sci. USA 98, 12521-
Torres, M., Gomez-Pardo, E. and Gruss, P. (1996). Pax2 contributes to inner
ear patterning and optic nerve trajectory. Development 122, 3381-3391.
Trousse, F., Marti, E., Gruss, P., Torres, M. and Bovolenta, P. (2001).
Control of retinal ganglion cell axon growth: a new role for Sonic hedgehog.
Development 128, 3927-3936.
Tucker, K. L., Meyer, M. and Barde, Y. A. (2001). Neurotrophins are
required for nerve growth during development. Nat. Neurosci. 4, 29-37.
Wang, Y., Thekdi, N., Smallwood, P. M., Macke, J. P. and Nathans, J.
(2002). Frizzled-3 is required for the development of major fiber tracts in
the rostral CNS. J. Neurosci. 22, 8563-8573.
Winberg, M. L., Tamagnone, L., Bai, J., Comoglio, P. M., Montell, D. and
Goodman, C. S. (2001). The transmembrane protein Off-track associates
with Plexins and functions downstream of Semaphorin signaling during
axon guidance. Neuron 32, 53-62.
Yoshikawa, S., McKinnon, R. D., Kokel, M. and Thomas, J. B. (2003). Wnt-
mediated axon guidance via the Drosophila Derailed receptor. Nature 422,
Development 132 (10)