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. 
OUR research is aimed at understanding the 
mechanisms that control cell patterning 
within the developing vertebrate nervous system. 
The major focus is on deciphering how discrete 
neural cell types appear at defined positions in 
the embryo. In addition, we are examining the 
roles of diffusible and cell surface molecules in 
the guidance of developing axons in the spinal 
cord. Our studies over the past several years have 
provided evidence that the floor plate, a special- 
ized group of neuroepithelial cells, has critical 
roles in both the control of cell identity and in 
axon guidance. Within the past year, further de- 
tails of the functions and molecular properties of 
the floor plate have become apparent. 
Control of Motor Neuron DiflFerentiation 
Our previous studies had shown that signals 
originating from the floor plate regulate the iden- 
tity of specific cell types within the neural tube. 
In order to examine in more detail the actions of 
the floor plate on neural cell patterning, we have 
begun to focus on one well-characterized neuron 
class, the spinal motor neuron. There is extensive 
information on the mechanisms that control the 
pathfinding of motor axons and the formation of 
synapses at the neuromuscular junction, but the 
events that control the generation of motor neu- 
rons remain largely obscure. 
Insight into the molecular mechanisms in- 
volved in the generation of motor neurons by 
floor plate-derived signals requires the identifi- 
cation of genes that are expressed at the initial 
stages of motor neuron differentiation. In collabo- 
ration with Thomas Edlund's laboratory in Umea, 
Sweden, we have found that embryonic chick 
motor neurons express a homeobox gene called 
Islet- 1 (Isl-1). This is a member of the subfamily 
of homeobox genes that contain cysteine-rich re- 
gions called LIM domains. Other members of the 
family include Lin- 11 and Mec-3, which have 
been shown to regulate cell fate in Caenorhab- 
ditis elegans. 
Isl- 1 binds to enhancer elements in the rat in- 
sulin gene and is expressed in pancreatic islet 
cells and in a subset of neurons, including motor 
neurons. In the embryonic chick spinal cord, 
Isl- 1 immunoreactivity is first detected in the nu- 
clei of cells in the ventral region, lateral to the 
floor plate. The number of Isl- 1* cells in the ven- 
tral spinal cord increases markedly during early 
spinal cord development. We established that the 
ventral spinal cord cells that express Isl- 1 are mo- 
tor neurons by retrograde injection of horserad- 
ish peroxidase (HRP) into motor axons in the 
ventral root. 
Analysis of the expression of motor neuron 
markers by chick spinal cord cells in vivo has 
provided evidence that the differentiation of mo- 
tor neurons is dependent on inductive signals 
from the floor plate. In agreement with this, the 
spinal cord of embryos that had received floor 
plate grafts contained additional ectopic Isl-1^ 
cells. The induced Isl-1^ cells also expressed the 
SCI glycoprotein and sent axons out of the spinal 
cord consistent with their identity as motor 
neurons. 
These results provide evidence that signals 
from the floor plate can induce the expression of 
Isl-1 in dorsal neural tube cells. Elimination of 
the notochord and floor plate before neural tube 
closure results in the development of a spinal 
cord devoid of ventral neuronal types, including 
motor neurons. Isl- 1 expression in the ventral spi- 
nal cord is also dependent on signals from the 
notochord and floor plate. These results support 
the idea that elimination of the notochord and 
floor plate prevents the initial steps in the differ- 
entiation of motor neurons. 
Homeobox genes are involved in many aspects 
of vertebrate development. The expression pat- 
tern of Hox genes along the anteroposterior axis 
of the neural tube, and of Pax genes along the 
dorsoventral axis, together with the phenotypes 
that result from inactivation of some of these 
genes, suggests that they contribute to the re- 
gional patterning of the developing nervous sys- 
tem. In contrast, the restricted expression of Isl-1 
and the involvement of related LIM-homeodo- 
main proteins in the determination of cell fate in 
C. elegans suggest that Isl- 1 may be involved in 
specifying the fate of specific neuronal subtypes 
— in particular, motor neurons. 
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