Control of Cell Fate During Vertebrate 
Neuronal Development 
David J. Anderson, Ph.D. — Assistant Investigator 
Dr. Anderson is also Associate Professor of Biology at the California Institute of Technology and Adjunct 
Assistant Professor of Anatomy and Cell Biology at the University of Southern California School of 
Medicine. He received his A.B. degree in biochemical sciences from Harvard College and a Ph.D. degree in 
cell biology from the Rockefeller University. He then did postdoctoral research in molecular neurobiology 
at Columbia University. He is the recipient of an NSF Presidential Young Investigator Award, a Sloan 
Foundation Fellowship in Neuroscience, and the 1989 Charles Judson Herrick Award in Neurobiology 
from the American Association of Anatomy. 
WE are interested in how different types of 
nerve cells are generated during the devel- 
opment of the vertebrate nervous system. We 
have chosen to work on the peripheral auto- 
nomic nervous system, which is simpler and 
more accessible than the brain. Our studies have 
focused on the development of two specific cell 
types: the sympathetic neurons that lie in a chain 
of ganglia along the spinal cord and the chromaf- 
fin cells of the adrenal medulla. These two cells 
are closely related, yet distinct in major respects. 
The former are true neurons, with long branching 
axons and dendrites that send and receive electri- 
cal signals. The latter are small, round secretory 
cells that release epinephrine (adrenaline) into 
the bloodstream during fright or excitement. 
Studies in a number of laboratories, including 
our own, have established that these two cell 
types derive from a common progenitor cell. This 
cell arises on top of the neural tube (the develop- 
ing spinal cord) , as part of a transient structure 
called the neural crest. Like parachutists, the 
neural crest cells peel off the neural tube in a 
wave and migrate downward through the em- 
bryo. Some of them arrest their migration in a 
chain of small clumps along a blood vessel, 
where they eventually become sympathetic neu- 
rons. Others continue their migration downward 
to invade the developing adrenal gland, where 
they become chromaffin cells. 
Using a sophisticated fluorescence-activated 
cell sorter and specific monoclonal antibodies to 
tag the cells, we have succeeded in isolating 
chromaffin cell precursors from the fetal adrenal 
gland of the rat. By manipulating the cell culture 
environment, we have shown that these precur- 
sors have two possible developmental fates: if 
glucocorticoid hormones are added to the 
growth medium, mimicking the environment of 
the adrenal gland, then the precursors develop 
into chromaffin cells. If, on the other hand, fibro- 
blast growth factor (FGF) and nerve growth fac- 
tor (NGF) are added to the medium, the precur- 
sors develop into sympathetic neurons. This 
suggests that the fate of these cells is determined 
in large part by signals in the environments to 
which they migrate. However, these precursors 
seem to have lost the ability to give rise to other 
derivatives of the neural crest, such as glial cells. 
Therefore, while these precursor cells have a 
choice of fate, it is a restricted one. 
Control of Neuronal Survival 
by Neurotrophic Factors 
One problem in studying the chromaffin-neu- 
ron precursor cell at the molecular level is the 
small number of cells that can be recovered after 
isolation from rat fetuses. To circumvent this 
problem, wc have applied recently developed 
techniques to immortalize the cells. Using a de- 
fective retrovirus as a "disposable molecular sy- 
ringe," we have injected the cells with a gene, 
v-myc, that allows them to divide forever in the 
culture dish. In this way we can generate an end- 
less supply of cells that can be used for experi- 
ments at any time, without the need to perform 
long hours of dissection. Fortunately, these im- 
mortalized precursor cell lines still appear capa- 
ble of undergoing differentiation into sympa- 
thetic neurons when exposed to FGF and NGF. 
Sympathetic neurons, like other neurons, de- 
pend on specific neurotrophic factors for their 
survival. Neurotrophic factors are proteins se- 
creted by the tissues innervated by the neurons; 
these proteins nourish the neurons and keep 
them alive. Different types of neurons use differ- 
ent neurotrophic factors: NGF is the factor for 
sympathetic neurons. The specificity of NGF ac- 
tion is due to a specific receptor protein present 
in the membrane of the nerve cell. This receptor 
binds NGF and sends a signal to the cell, keeping 
it alive. We are using the immortalized precursor 
cell line to study how developing neurons ac- 
quire NGF receptors during development. The 
NGF receptor has two components (subunits); 
our data suggest that different factors induce the 
expresision of these two subunits. One factor that 
seems to be important for the induction of func- 
tional NGF receptors is electrical activity. This 
suggests that the stimulation of the developing 
