Global Control of Motor Neuron Topography Mediated by the Repressive Actions of a Single Hox Gene

Heekyung Jung, Julie Lacombe, Esteban O. Mazzoni, Karel F. Liem, Jonathan Grinstein, Shaun Mahony, Debnath Mukhopadhyay, David K. Gifford, Richard A. Young, Kathryn V. Anderson, Hynek Wichterle, Jeremy S. Dasen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)781-796
Number of pages16
JournalNeuron
Volume67
Issue number5
DOIs
StatePublished - Sep 2010

Fingerprint

Homeobox Genes
Motor Neurons
Extremities
Thorax
Forelimb
Chromatin
Spinal Cord
Transcription Factors
Genome
Neurons
Population

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Global Control of Motor Neuron Topography Mediated by the Repressive Actions of a Single Hox Gene. / Jung, Heekyung; Lacombe, Julie; Mazzoni, Esteban O.; Liem, Karel F.; Grinstein, Jonathan; Mahony, Shaun; Mukhopadhyay, Debnath; Gifford, David K.; Young, Richard A.; Anderson, Kathryn V.; Wichterle, Hynek; Dasen, Jeremy S.

In: Neuron, Vol. 67, No. 5, 09.2010, p. 781-796.

Research output: Contribution to journalArticle

Jung, H, Lacombe, J, Mazzoni, EO, Liem, KF, Grinstein, J, Mahony, S, Mukhopadhyay, D, Gifford, DK, Young, RA, Anderson, KV, Wichterle, H & Dasen, JS 2010, 'Global Control of Motor Neuron Topography Mediated by the Repressive Actions of a Single Hox Gene', Neuron, vol. 67, no. 5, pp. 781-796. https://doi.org/10.1016/j.neuron.2010.08.008
Jung, Heekyung ; Lacombe, Julie ; Mazzoni, Esteban O. ; Liem, Karel F. ; Grinstein, Jonathan ; Mahony, Shaun ; Mukhopadhyay, Debnath ; Gifford, David K. ; Young, Richard A. ; Anderson, Kathryn V. ; Wichterle, Hynek ; Dasen, Jeremy S. / Global Control of Motor Neuron Topography Mediated by the Repressive Actions of a Single Hox Gene. In: Neuron. 2010 ; Vol. 67, No. 5. pp. 781-796.
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