MOLECULAR MECHANISMS OF VERTEBRATE NEURONAL DEVELOPMENT 
Thomas M. Jessell, Ph.D., Investigator 
Dr. Jessell's laboratory continues to focus on cel- 
lular and molecular mechanisms that control the 
differentiation and early development of the verte- 
brate nervous system. 
I. Cell Differentiation in the Neural Tube. 
In vertebrates, the patterning of the central ner- 
vous system begins soon after induction of the neu- 
ral plate. The regional specification of the neural 
tube is imposed by local cell interactions that regu- 
late cell differentiation. Dr. Jessell and his col- 
leagues have examined the contribution of a group 
of epithelial cells located at the axial midline of the 
neural plate, named the floor plate, to cell pattern- 
ing v^^ithin the neural tube. 
Studies performed in collaboration with Drs. 
Gregor Eichele and Christina Thaller (Harvard Med- 
ical School) have shown that the floor plate is the 
source of a morphogen that polarizes developing 
embryonic tissues. Cells of the floor plate, but not 
other regions of the neural tube, evoke digit redu- 
plications when transplanted into the anterior re- 
gion of the chick limb bud. This mimics the 
morphogenetic activity of a region of the limb 
known as the zone of polarizing activity (ZPA). Evi- 
dence indicates that the ZPA morphogen that speci- 
fies limb polarity and digit pattern is retinoic acid. 
These findings suggest that the floor plate is a focal 
source of retinoic acid within the developing neural 
tube. In support of this. Dr. Jessell and his collabo- 
rators have found that the floor plate possesses a 
greater capacity to convert the metabolic precursor 
retinol to retinoic acid than other regions of the 
spinal cord. The role of the retinoic acid-like 
morphogen in the floor plate may be to regulate 
the differentiation of adjacent neuroepithelial cells 
and impose pattern along the dorsoventral axis of 
the neural tube. 
Dr. Jessell and his colleagues have also shown 
that at later developmental stages the floor plate re- 
leases a diffusible chemotropic factor that orients 
the growth of developing spinal neurons. Evidence 
that the floor plate releases a chemotropic factor 
that guides commissural spinal axons was obtained 
by coculturing explants of Ell rat floor plate and 
dorsal neural tube in a collagen gel matrix capable 
of stabilizing gradients of diffusible factors. Dorsal 
spinal cord explants grown in the absence of a 
floor plate target exhibited little or no axon out- 
growth. In contrast, in the presence of a floor plate 
there was profuse axon outgrowth from the dorsal 
explant oriented toward the floor plate. The axons 
that extend from dorsal explants appear to derive 
from commissural neurons, since they express the 
cell surface glycoprotein TAG-1, which is selectively 
expressed by commissural axons. 
The factor released by the floor plate is selective 
for commissural axons and does not affect the pat- 
tern of growth of association, motor, or sensory 
axons. Moreover, the induction of commissural 
axon outgrowth from dorsal explants is highly spe- 
cific to the floor plate. Other neural and nonneural 
embryonic tissues, including the remainder of the 
Ell neural tube and notochord, do not exhibit 
activity. The action of the floor plate is not mim- 
icked by defined growth factors and may therefore 
reflect the presence of a novel chemotropic mole- 
cule. Studies to characterize this molecule are in 
progress. 
The analysis of axon pathfinding in Danforth 
short tail mice, which lack a floor plate, provided 
additional evidence that the floor plate guides com- 
missural axons. In collaboration with Dr. Jane 
Dodd, commissural axons in affected embryos have 
been shown to exhibit marked perturbations in 
axon trajectory at the ventral midline, in the region 
normally occupied by the floor plate. Commissural 
axons project out of the spinal cord, forming a su- 
pernumerary nerve that exhibits abnormal projec- 
tions. 
These observations provide evidence that the 
floor plate regulates neuronal differentiation in sev- 
eral ways: 1) by releasing a polarizing morphogen, 
2) by releasing a diffusible chemotropic factor, and 
3) by acting as an intermediate target involved in 
contact guidance. 
II. Axonal Glycoproteins Involved in Neuronal 
Recognition. 
The molecular basis of pathway selection by de- 
veloping spinal axons has also been studied. One 
mechanism of growth cone guidance appears to in- 
volve interactions between glycoproteins on the sur- 
face of axons and cell surface or matrix molecules 
in their environment. The 135 kDa axonal glycopro- 
tein TAG-1 that is expressed transiently on subsets 
of developing axons and may be involved in the ini- 
tial stages of axonal growth has been identified. 
To provide further information on the structure 
and function of TAG-1, Dr. Jessell and his col- 
Continued 
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