TY - JOUR
T1 - Global Control of Motor Neuron Topography Mediated by the Repressive Actions of a Single Hox Gene
AU - Jung, Heekyung
AU - Lacombe, Julie
AU - Mazzoni, Esteban O.
AU - Liem, Karel F.
AU - Grinstein, Jonathan
AU - Mahony, Shaun
AU - Mukhopadhyay, Debnath
AU - Gifford, David K.
AU - Young, Richard A.
AU - Anderson, Kathryn V.
AU - Wichterle, Hynek
AU - Dasen, Jeremy S.
N1 - Funding Information:
We thank Tom Jessell, Gord Fishell, and members of the lab for comments on the manuscript. Mario Capecchi and Deneen Wellik provided Hox mutant lines, Tom Jessell provided Olig2::Cre mice, and Silvia Arber provided Pea3 antibodies. We thank NYU transgenic facility for mouse husbandry, and Brian Dynlacht for help with the in vivo ChIP assays. E.O.M. is the David and Sylvia Lieb Fellow of the Damon Runyon Cancer Research Foundation, DRG-1937-07. K.L. and K.A. are supported by grants from Project ALS and NIH R01 NS044385. S.M., D.M., D.K.G., R.A.Y., and H.W. are supported by NIH P01 NS055923. J.D. is supported by grants from the Alfred P. Sloan Foundation, Burroughs Welcome Fund, McKnight Foundation, NIH R01 NS062822, NYStem and Project ALS. J.D. is an HHMI Early Career Scientist.
PY - 2010/9
Y1 - 2010/9
N2 - In the developing spinal cord, regional and combinatorial activities of Hox transcription factors are critical in controlling motor neuron fates along the rostrocaudal axis, exemplified by the precise pattern of limb innervation by more than fifty Hox-dependent motor pools. The mechanisms by which motor neuron diversity is constrained to limb levels are, however, not well understood. We show that a single Hox gene, Hoxc9, has an essential role in organizing the motor system through global repressive activities. Hoxc9 is required for the generation of thoracic motor columns, and in its absence, neurons acquire the fates of limb-innervating populations. Unexpectedly, multiple Hox genes are derepressed in Hoxc9 mutants, leading to motor pool disorganization and alterations in the connections by thoracic and forelimb-level subtypes. Genome-wide analysis of Hoxc9 binding suggests that this mode of repression is mediated by direct interactions with Hox regulatory elements, independent of chromatin marks typically associated with repressed Hox genes.
AB - In the developing spinal cord, regional and combinatorial activities of Hox transcription factors are critical in controlling motor neuron fates along the rostrocaudal axis, exemplified by the precise pattern of limb innervation by more than fifty Hox-dependent motor pools. The mechanisms by which motor neuron diversity is constrained to limb levels are, however, not well understood. We show that a single Hox gene, Hoxc9, has an essential role in organizing the motor system through global repressive activities. Hoxc9 is required for the generation of thoracic motor columns, and in its absence, neurons acquire the fates of limb-innervating populations. Unexpectedly, multiple Hox genes are derepressed in Hoxc9 mutants, leading to motor pool disorganization and alterations in the connections by thoracic and forelimb-level subtypes. Genome-wide analysis of Hoxc9 binding suggests that this mode of repression is mediated by direct interactions with Hox regulatory elements, independent of chromatin marks typically associated with repressed Hox genes.
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U2 - 10.1016/j.neuron.2010.08.008
DO - 10.1016/j.neuron.2010.08.008
M3 - Article
C2 - 20826310
AN - SCOPUS:77956334497
SN - 0896-6273
VL - 67
SP - 781
EP - 796
JO - Neuron
JF - Neuron
IS - 5
ER -