Control of Cell Pattern in 
the Developing Nervous System 
Thomas M. Jessell, Ph.D. — Investigator 
Dr. Jessell is also Professor of Biochemistry and Molecular Biophysics at Columbia University College of 
Physicians and Surgeons and a member of the Center for Neurobiology and Behavior. He received his 
Ph.D. degree in neurobiology from Cambridge University, England, and was elected a research fellow of 
Cambridge's Trinity College. He was a postdoctoral fellow in Gerald Fischbach's laboratory at Harvard 
Medical School. Next he served as Assistant Professor of Neurobiology at Harvard Medical School, before 
moving to Columbia University. 
A major aim of our research is to define the 
mechanisms that control the patterning of 
neural tissues in vertebrate embryos. Our studies 
continue to focus on the events contributing to 
the differentiation of specific cell types in the 
developing neural tube. Over the past year we 
have obtained evidence that the floor plate, a spe- 
cialized group of neuroepithelial cells, is in- 
volved in establishing the pattern of cell differen- 
tiation along the dorsoventral (D-V) axis of the 
central nervous system. 
The development of the vertebrate nervous sys- 
tem begins v^ith induction of the neural plate, 
followed by differentiation of distinct cell types 
at different positions along the D-V axis of the 
neural tube. For example, in the spinal cord, mo- 
tor neurons are located ventrally, whereas com- 
missural neurons and neural crest cells appear in 
dorsal positions. The distribution of each of these 
cell types is bilaterally symmetric with reference 
to the midline of the neural tube. 
Cells at the midline of the neural plate cells 
give rise to a specialized region called the floor 
plate. In collaboration with Jane Dodd's labora- 
tory, we have developed functional assays show- 
ing that the floor plate differentiation is induced 
by underlying mesodermal cells of the noto- 
chord. We have also found that specialized prop- 
erties of the floor plate cells influence the devel- 
opment of other neural cells. A diffusible 
chemoattractant released by the floor plate or- 
ients the growth of a subset of developing spinal 
cord axons. In addition, the floor plate and the 
notochord are sources of a polarizing signal that 
respecifies cell pattern along the anterior-poste- 
rior (A-P) axis of the developing chick limb, mim- 
icking the effect of the putative morphogen reti- 
noic acid. 
These findings raised the possibility that the 
floor plate and notochord may also be involved in 
controlling the patterning of cell differentiation 
along the D-V axis of the developing nervous sys- 
tem. To test this possibility, we have used anti- 
bodies directed against cell-specific antigens to 
determine whether the pattern of cells in the em- 
bryonic chick nervous system changes after a) 
induction of an additional floor plate at ectopic 
positions in the neural tube by a notochord graft 
or b) grafting of a floor plate next to the neural 
tube or c) removal of the notochord to prevent 
floor plate differentiation. Such manipulations 
cause marked changes in the fate and position of 
neural cell types. For example, a and b result in 
the appearance of ectopic motor neurons, and c 
results in the absence of motor neurons. 
Our results suggest that the pattern of cell dif- 
ferentiation within the neural tube is established 
by signals originating at the floor plate and noto- 
chord. For example, the notochord and floor 
plate could act as local sources of a factor that 
diffuses through the adjacent neural epithelium, 
establishing a concentration gradient with its 
high point at the ventral midline. In this scheme, 
the differentiation of neural epithelial cells into 
distinct classes during normal development 
would be controlled by the signal concentration 
to which they are exposed. 
A similar gradient model has been proposed to 
explain the pattern of cell differentiation along 
the A-P axis of the developing chick wing bud. 
A-P pattern in the bud appears to be under the 
control of a specialized region of posterior mesen- 
chyme known as the zone of polarizing activity 
(ZPA), which can respecify A-P polarity when 
grafted to ectopic sites. Retinoic acid mimics the 
effects of the ZPA and appears to be distributed in 
a graded manner along the A-P axis of the limb 
bud, with its highest concentration in the poste- 
rior mesenchyme. On this basis, it has been sug- 
gested that retinoic acid functions as an endoge- 
nous morphogen involved in establishing axial 
polarity in the developing chick limb. 
The notochord and floor plate, but not other 
regions of the neural tube, mimic the action of 
the ZPA and retinoic acid in respecifying digit 
pattern in the chick limb. Moreover, our bio- 
chemical studies show that the floor plate can 
synthesize morphogenetically active retinoids in 
vitro. The ability of the notochord and floor plate 
to control the pattern of cell differentiation in 
both the developing limb bud and the neural 
tube may therefore have a common molecular 
basis, possibly involving retinoids. 
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