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The Journal of Neuroscience, February 1, 2001, 21(3):911-919
Deleted in Colorectal Cancer (DCC) Regulates the Migration
of Luteinizing Hormone-Releasing Hormone Neurons to the Basal
Forebrain
Gerald A.
Schwarting1, 2,
Christine
Kostek1,
Elizabeth P.
Bless1,
Naira
Ahmad1, and
Stuart A.
Tobet1, 3
1 The Shriver Center, Waltham, Massachusetts 02452, and
Departments of 2 Cell Biology and 3 Physiology,
University of Massachusetts Medical School, Worcester, Massachusetts
01655
Luteinizing hormone-releasing hormone (LHRH) neurons migrate from
the vomeronasal organ (VNO) to the forebrain in all mammals studied. In
mice, most LHRH neuron migration is dependent on axons that originate
in the VNO but bypass the olfactory bulb and project into the basal
forebrain. Thus, cues that regulate the trajectories of these
vomeronasal axons are candidates for determining the destination of
LHRH neurons. Using in situ hybridization techniques, we
examined the expression of Deleted in colorectal cancer (DCC), a
vertebrate receptor for the guidance molecule netrin-1, during development of the olfactory system. DCC is expressed by cells in the
olfactory epithelium (OE) and VNO, and in cells migrating from the OE
and VNO from embryonic day 11 (E11) to E14. Some
DCC+ cells on vomeronasal axons in the nose also
express LHRH. However, DCC expression is downregulated beginning at
E12, so few if any LHRH neurons in the forebrain also express DCC. In
rat, DCC is expressed on TAG-1+ axons that guide
migrating LHRH neurons. We therefore examined LHRH neuron migration in
DCC / mice and found that
trajectories of the caudal vomeronasal nerve and positions of LHRH
neurons are abnormal. Fewer than the normal number of LHRH neurons are
found in the basal forebrain, and many LHRH neurons are displaced into
the cerebral cortex of DCC/
mice. These results are consistent with the idea that DCC regulates the
trajectories of a subset of vomeronasal axons that guide the migration
of LHRH neurons. Loss of DCC function results in the migration of many
LHRH neurons to inappropriate destinations.
Key words:
DCC; luteinizing hormone-releasing hormone; axon
guidance; cell migration; vomeronasal; olfactory
Copyright © 2001 Society for Neuroscience 0270-6474/01/213911-09$05.00/0
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