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The Journal of Neuroscience, March 1, 2003, 23(5):1769
Widespread Defects in the Primary Olfactory Pathway Caused by
Loss of Mash1 Function
Richard C.
Murray1, 3,
Daniel
Navi1, 3,
John
Fesenko2, 3,
Arthur D.
Lander2, 3, and
Anne L.
Calof1, 3
1 Department of Anatomy and Neurobiology,
2 Department of Developmental and Cell Biology, and
3 Developmental Biology Center, University of California,
Irvine, Irvine, California 92697-2300
MASH1, a basic helix-loop-helix transcription factor, is widely
expressed by neuronal progenitors in the CNS and PNS, suggesting that
it plays a role in the development of many neural regions. However, in
mice lacking a functional Mash1 gene, major alterations have been reported in only a few neuronal populations; among these is a
generalized loss of olfactory receptor neurons of the olfactory epithelium. Here, we use a transgenic reporter mouse line, in which the
cell bodies and growing axons of subsets of central and peripheral
neurons are marked by expression of a tau-lacZ reporter
gene (the Tattler-4 allele), to look both more broadly and deeply at defects in the nervous system of Mash1 /
mice. In addition to the expected lack of olfactory receptor
neurons in the main olfactory epithelium, developing
Mash1/;Tattler-4+/ mice exhibited reductions in
neuronal cell number in the vomeronasal organ and in the olfactory
bulb; the morphology of the rostral migratory stream, which gives rise
to olfactory bulb interneurons, was also abnormal. Further examination
of cell proliferation, cell death, and cell type-specific markers in
Mash1/ animals uncovered parallels between the main
olfactory epithelium and the vomeronasal organ in the regulation of
sensory neuron development. Interestingly, this analysis also revealed
that, in the olfactory epithelium of Mash1/ animals,
there is an overproduction of proliferating cells that co-express
markers of both neuronal progenitors and supporting cells. This finding
suggests that olfactory receptor neurons and olfactory epithelium
supporting cells may share a common progenitor, and that expression of
Mash1 may be an important factor in determining whether
these progenitors ultimately generate neurons or glia.
Key words:
bHLH transcription factor; olfactory epithelium; olfactory receptor neuron; transgenic mouse; olfactory bulb; rostral
migratory stream; subventricular zone; vomeronasal organ; neural
progenitor; lineage; supporting cell; granule cell
Copyright © 2003 Society for Neuroscience 0270-6474/03/2351769-12$05.00/0
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