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First published online 29 September 2004
doi: 10.1242/dev.01416
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1 Department of Molecular Biology, Umeå University, Umeå, SE901 87,
Sweden
2 Umea Centre for Molecular Medicine, Umeå University, Umeå, SE901
87, Sweden
* Author for correspondence (e-mail: staffan.bohm{at}molbiol.umu.se)
Accepted 17 August 2004
Progenitor cells in the mouse olfactory epithelium generate over a thousand
subpopulations of neurons, each expressing a unique odorant receptor (OR)
gene. This event is under the control of spatial cues, since neurons in
different epithelial regions are restricted to express region-specific subsets
of OR genes. We show that progenitors and neurons express the LIM-homeobox
gene Lhx2 and that neurons in Lhx2-null mutant embryos do
not diversify into subpopulations expressing different OR genes and other
region-restricted genes such as Nqo1 and Ncam2.
Lhx2-/- embryos have, however, a normal distribution of
Mash1-positive and neurogenin 1-positive neuronal progenitors that leave the
cell cycle, acquire pan-neuronal traits and form axon bundles. Increased cell
death in combination with increased expression of the early differentiation
marker Neurod1, as well as reduced expression of late differentiation
markers (G
olf and Omp), suggests that neuronal
differentiation in the absence of Lhx2 is primarily inhibited at, or immediate
prior to, onset of OR expression. Aberrant regional expression of early and
late differentiation markers, taken together with unaltered region-restricted
expression of the Msx1 homeobox gene in the progenitor cell layer of
Lhx2-/- embryos, shows that Lhx2 function is not required
for all aspects of regional specification of progenitors and neurons. Thus,
these results indicate that a cell-autonomous function of Lhx2 is required for
differentiation of progenitors into a heterogeneous population of individually
and regionally specified mature olfactory sensory neurons.
Key words: Lhx2, Neurod1, Olfactory, Gene expression, Odorant receptors, Lim, Homeobox, Neuron, Differentiation, Mouse
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