CONTROL OF CELL PATTERN IN VERTEBRATE NEURAL DEVELOPMENT 
Thomas M. Jessell, Ph.D., Investigator 
Research in Dr. Jessell 's laboratory continues to 
focus on two aspects of neural development in ver- 
tebrates-, defining the interactions that control cell 
identity and regional pattern during the initial 
stages of neural development, and characterizing 
the molecules and mechanisms that guide develop- 
ing axons. 
Control of Neural Cell Identity and Pattern 
The development of the nervous system begins 
with the induction of the neural plate from uncom- 
mitted ectodermal cells in response to signals from 
mesoderm. As the neural plate folds to form the 
neural tube, distinct classes of cells appear in a bilat- 
erally symmetric manner at different dorsal -ventral 
(D-V) positions. This pattern is conserved at differ- 
ent segmental levels of the spinal cord, suggesting 
that cell identity in this region is defined primarily 
by position along the D-V axis of the neural tube. 
Studies by Dr. Toshiya Yamada, in collaboration 
with Drs. Marysia Placzek and Jane Dodd, have sug- 
gested that the bilateral organization and D-V pat- 
tern of cell types is established by signals derived 
from cells at the midline of the neural plate. In vivo 
grafting studies and in vitro assays that monitor 
functional and biochemical markers of the floor 
plate have shown that the differentiation of neuroep- 
ithelial cells into floor plate is induced by contact 
with the notochord. Strikingly, the newly induced 
floor plate acquires the inductive properties of the 
notochord, including the ability to induce floor 
plate difi'erentiation. This self-inductive signal may 
be important in recruiting cells into the floor plate 
from more lateral regions of the neural plate. 
The floor plate and notochord appear to control 
the position and identity of motor neurons and other 
ventral spinal cord neurons. Grafts of notochord or 
floor plate next to the neural tube induce the ap- 
pearance of ectopic motor neurons and other ven- 
tral neurons, defined by cell-specific markers. In- 
versely, removal of the notochord and floor plate 
prevents the differentiation of these neuronal types. 
In contrast to the contact dependence of floor plate 
induction, the differentiation of motor neurons in 
vitro can be initiated by diffusible signals from the 
floor plate and notochord. These findings suggest 
that D-V patterning in the spinal cord is dependent 
on a cascade of inductive interactions, initiated by 
the notochord and continued by the floor plate. 
Genes that control cell identity in the neural 
tube. Studies to identify genes that might contribute 
to the determination of cell identity in the neural 
tube have focused on two classes of molecules: tran- 
scription factors and peptide growth factors. 
Dr. Ariel Ruiz i Altaba has shown that cells at the 
midline of the neural plate that later become the 
floor plate express DNA-binding proteins related to 
the rat HNF-3 and the Drosophila fork head gene 
families. Overexpression of one of these genes, Pin- 
tallavis, in Xenopus embryos leads to the expres- 
sion of a floor plate-specific gene, F-spondin, in 
dorsal regions of the spinal cord and to the loss of 
dorsal cell types. These results suggest that Pintal- 
lavis contributes to the specification of floor plate 
properties. 
Studies by Dr. Yamada, in collaboration with the 
laboratory of Dr. Thomas Edlund, have shown that 
developing motor neurons express the Islet- 1 gene, 
a member of the LIM-homeodomain family. Islet- 1 
expression occurs soon after the final division of 
motor neurons but before the onset of expression of 
other neuron markers, suggesting that the gene may 
control some of the later phenotypic properties of 
motor neurons. 
There is increasing evidence that secreted growth 
factors of the transforming growth factor-|8 (TGF-|8), 
Wnt, and fibroblast growth factor (FGF) families 
may control neural cell identity and pattern. Dr. 
Konrad Easier and Dr. Yamada have identified a 
novel member of the TGF-jS superfamily, Dorsalin, 
which is selectively expressed in the dorsal region 
of the neural tube. Grafting experiments show that 
signals from the notochord and floor plate appear to 
restrict Dorsalin expression to the dorsal spinal 
cord. The localized expression of the Dorsalin gene 
may be required for the differentiation of cell types 
found in the dorsal region of the neural tube. 
In addition, repression of Dorsalin expression in 
ventral regions may be a prerequisite for the differ- 
entiation of ventral cell types such as motor neu- 
rons. In support of this idea, Dorsalin prevents the 
differentiation of motor neurons in vitro in re- 
sponse to notochord and floor plate-derived sig- 
nals. Dorsalin may block motor neuron differentia- 
tion by causing ventral neural tube cells to acquire 
dorsal cell fates or may arrest neuroepithelial cell 
differentiation. 
Regulation of Axonal Pathfinding 
in the Central Nervous System 
The projection of axons to their targets along 
complex but stereotyped pathways is initiated soon 
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