In Brain Development Identified
Astrotactin Is A Nerve's Ticket To Ride The Glial
N.Y. (4/22/96) -- Scientists from The Rockefeller University and
the Howard Hughes Medical Institute (HHMI) have for the first
time identified a gene involved in directing nerve cells to their
destinations as the brain grows. Their work appears in the April
"The gene we discovered
makes a protein, astrotactin, required for young neurons to migrate
along glial fibers to find their correct positions in the growing
brain. This journey is important because it is the way young neurons
gain their identity," says Mary E. Hatten, Ph.D., head of the Laboratory
of Developmental Neurobiology at Rockefeller. "Knowing the gene's
function could lead to a greater understanding of epilepsy, a condition
people can be born that we think occurs because of problems with
Hatten and her coauthors'
findings also may shed light on the development of childhood brain
tumors, learning disabilities, schizophrenia and degenerative brain
disorders in the elderly. Already, researchers know that exposure
to alcohol, cocaine and radiation can hinder the migration of neurons
during fetal development.
In the new study, Hatten
and her colleagues found a gene, Astrotactin, in the neurons of
mice that contains the instructions to make the astrotactin protein.
Neurons use the protein, which Hatten discovered, to grab hold of
fibers in the developing brain and move along them.
The migration of neurons
is critical to survival. During the development of the fetus, cells
form a tube that will grow into the brain and spinal cord. After
cells are born, they move through the tube's thickening wall to
form the layers of what will be the cortex, the brain's outer layer
known as gray matter. By completing this journey the neurons develop
and organize into the brain's architecture.
The migration of young
neurons in the brain's cerebellar cortex, which controls movement
and balance, continues until a child reaches the age of two. Although
a neuron's journey along the glial fiber highway is just a few millimeters,
this distance is comparable to a person traveling from New York
City to Chicago, Hatten says. The nerve cells can migrate at speeds
of 20 to 50 microns per hour- about one thousandth of an inch, which
is considered fast for a neuron.
In addition the cerebellum,
the researchers pinpointed active Astrotactin genes in the brain's
cortex, hippocampus and olfactory system, responsible for thinking,
memory and smelling.
Hatten and her coinvestigators
also identified a second function of astrotactin. "The astrotactin
protein helps glial cells to sustain their health and identity,"
explains coauthor Nathaniel Heintz, Ph.D., head of the Laboratory
of Molecular Biology at Rockefeller and an HHMI investigator. "Without
a connection to astrotactin, the glial cells collapse. In contrast,
astrotactin is not essential to maintaining the health of neurons."
With the cloning of the
Astrotactin gene, the research team proposes that at least three
genes play a role in the migration and assembly of neurons during
the development of the cortical areas of the brain in mice: the
Astrotactin gene, the Weaver gene and the Reeler gene. However,
Weaver and Reeler occur as the result of mutations and they interfere
with migration. Weaver prevents astrotactin production in the neuron
and Reelin disturbs the organization of neurons at the end of their
Hatten and Heintz's coauthor
is Chen Zheng, B.S. The National Institute of Neurological Disorders
and Stroke supported the study. Hatten's work also is funded by
a McKnight Neuroscience Award.
Rockefeller began in
1901 as the Rockefeller Institute for Medical Research, the first
U.S. biomedical research center. Rockefeller faculty members have
made significant scientific achievements, including the discovery
that DNA is the carrier of genetic information and the launching
of the scientific field of modern cell biology. The university has
ties to 19 Nobel laureates, including the president, Torsten N.
Wiesel, M.D., who received the prize in 1981. Recently, the university
created four centers to foster collaborations among scientists to
pursue investigations of Alzheimer's Disease, human genetics, neurosciences
and the links between physics and biology.