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First published online August 7, 2009
doi: 10.1242/10.1242/dev.037986


Development 136, 2923-2932 (2009)
Published by The Company of Biologists 2009


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Islet-to-LMO stoichiometries control the function of transcription complexes that specify motor neuron and V2a interneuron identity

Mi-Ryoung Song1,2,*, Yunfu Sun3, Ami Bryson2, Gordon N. Gill3, Sylvia M. Evans3 and Samuel L. Pfaff2,*

1 Bioimaging Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
2 Howard Hughes Medical Institute and Gene Expression Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
3 Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

* Authors for correspondence (msong{at}gist.ac.kr; pfaff{at}salk.edu)

Accepted 23 June 2009

LIM transcription factors bind to nuclear LIM interactor (Ldb/NLI/Clim) in specific ratios to form higher-order complexes that regulate gene expression. Here we examined how the dosage of LIM homeodomain proteins Isl1 and Isl2 and LIM-only protein Lmo4 influences the assembly and function of complexes involved in the generation of spinal motor neurons (MNs) and V2a interneurons (INs). Reducing the levels of Islet proteins using a graded series of mutations favored V2a IN differentiation at the expense of MN formation. Although LIM-only proteins (LMOs) are predicted to antagonize the function of Islet proteins, we found that the presence or absence of Lmo4 had little influence on MN or V2a IN specification. We did find, however, that the loss of MNs resulting from reduced Islet levels was rescued by eliminating Lmo4, unmasking a functional interaction between these proteins. Our findings demonstrate that MN and V2a IN fates are specified by distinct complexes that are sensitive to the relative stoichiometries of the constituent factors and we present a model to explain how LIM domain proteins modulate these complexes and, thereby, this binary-cell-fate decision.

Key words: LIM transcription factor, Motor neuron, V2a interneuron, Cell-fate specification, Ldb (NLI, CLIM, Chip), Lmo4, Isl1, Isl2, Lhx3, Mouse, Chick


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