after the commitment of cells to a particular neuro- 
nal fate. Studies in Dr. Jessell's laboratory have fo- 
cused on the mechanisms that control the growth 
and guidance of axons of commissural neurons in 
the developing spinal cord. The complex trajectory 
of commissural axons appears to reflect the opera- 
tion of several distinct cues that guide axons over 
discrete segments of their overall path. 
Commissural axons express the cell surface gly- 
coprotein TAG- 1 . Molecular cloning of TAG- 1 re- 
vealed that it is a member of the immunoglobulin 
superfamily closely related to LI and NCAM (neural 
cell adhesion molecule). In contrast to LI and most 
forms of NCAM, TAG- 1 is attached to the axonal sur- 
face by a lipid anchor and is also released from cells 
in large amounts, suggesting that the protein is pres- 
ent in the environment of extending commissural 
axons. Studies by Drs. Andrev^ Furley, Mary Hynes, 
and Dan Felsenfeld have found that TAG- 1 can pro- 
mote cell aggregation by a homophilic interaction 
but promotes neurite outgrowth by a heterophilic 
interaction, possibly with members of the integrin 
family. Since TAG-1 is likely to be released from 
pioneering commissural axons, it may provide a 
local substrate that both promotes and restricts 
spatially the growth of later differentiating com- 
missural axons. The guidance of pioneering 
commissural axons appears, however, to be depen- 
dent on cues other than TAG-1, including a floor 
plate-derived chemoattractant. 
When commissural axons reach the contralateral 
boundary of the rat floor plate, they turn orthogo- 
nally and grow parallel to the longitudinal edge of 
the floor plate in a rostral direction. This change in 
trajectory is accompanied by the loss of TAG-1 from 
the axonal surface, the onset of expression of high 
levels of LI , and a marked increase in axon fascicula- 
tion. These changes occur in contact with the floor 
plate, raising the possibility that cell surface or ex- 
tracellular matrix molecules synthesized by the 
floor plate might mediate these events, either through 
adhesive interactions or intercellular signaling. 
Studies by Drs. Avihu Klar and Jochen Walter have 
begun to characterize adhesion or signaling mole- 
cules expressed selectively by the floor plate. Molec- 
ular cloning has identified two novel proteins that 
are expressed at high levels by the floor plate over 
the period of commissural axon growth. The first, 
F-spondin, is a secreted protein that exhibits homol- 
ogy to the extracellular matrix glycoprotein throm- 
bospondin and to other adhesive proteins. The 
second, FP-84, is a transmembrane protein that is a 
novel member of the immunoglobulin family. Both 
F-spondin and FP-84 have neurite outgrowth- 
promoting activity. The restricted expression of 
these two proteins on the surface of the floor plate 
or in the extracellular matrix may contribute to the 
changes in guidance and behavior of commissural 
axons at the ventral midline of the spinal cord. 
Dr. Jessell is also Professor of Biochemistry and 
Molecular Biophysics and a member of the Center 
for Neurobiology and Behavior at the Columbia 
University College of Physicians and Surgeons. 
Articles 
Ericson, J., Thor, S., Edlund, T., Jessell, T.M., and 
Yamada, T. 1992. Early stages of motor neuron 
difi'erentiation revealed by expression of homeo- 
box gene Islet-1. Science 256:1555-1560. 
Jessell, T.M., and Dodd, J. 1992. Floor plate- 
derived signals and the control of neural cell pat- 
tern in vertebrates. Harvey Lect 86:87-1 28. 
Jessell, T.M., and Melton, D.A. 1992. Diffusible fac- 
tors in vertebrate embryonic induction. Cell 
68:257-270. 
Klar, A., Baldassare, M., and Jessell, T.M. 1992. 
F-spondin: a gene expressed at high levels in the 
floor plate encodes a secreted protein that pro- 
motes neural cell adhesion and neurite extension. 
Ce// 69:95-110. 
Placzek, M., Yamada, T., Tessier-Lavigne, M., Jes- 
sell, T.M., and Dodd, J. 1991. Control of dorso- 
ventral pattern in vertebrate neural development: 
induction and polarizing properties of the floor 
plate. Dev Suppl 2:105-122. 
Rathjen, FJ., and Jessell, T.M. 1991. Glycoproteins 
that regulate the growth and guidance of verte- 
brate axons: domains and dynamics of the immu- 
noglobulin/fibronectin III family. Semin Neuro- 
5a 3:297-307. 
NEUROSCIENCE 415 
