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Dev Cell. 2014 Apr 28;29(2):171-87. doi: 10.1016/j.devcel.2014.03.008. Epub 2014 Apr 17.

Evolving Hox activity profiles govern diversity in locomotor systems.

Author information

1
Howard Hughes Medical Institute, NYU Neuroscience Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016, USA.
2
Department of Biology, New York University, New York, NY 10003, USA.
3
Department of Genetics and Evolution, University of Geneva, Sciences III, Quai Ernest-Ansermet 30, 1211 Geneva 4, Switzerland; Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany.
4
Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A(∗)STAR, Biopolis, Singapore 138673, Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
5
Department of Genetics and Evolution, University of Geneva, Sciences III, Quai Ernest-Ansermet 30, 1211 Geneva 4, Switzerland; School of Life Sciences, Ecole Polytechnique Fédérale, 1015 Lausanne, Switzerland.
6
Howard Hughes Medical Institute, NYU Neuroscience Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: jeremy.dasen@nyumc.org.

Abstract

The emergence of limb-driven locomotor behaviors was a key event in the evolution of vertebrates and fostered the transition from aquatic to terrestrial life. We show that the generation of limb-projecting lateral motor column (LMC) neurons in mice relies on a transcriptional autoregulatory module initiated via transient activity of multiple genes within the HoxA and HoxC clusters. Repression of this module at thoracic levels restricts expression of LMC determinants, thus dictating LMC position relative to the limbs. This suppression is mediated by a key regulatory domain that is specifically found in the Hoxc9 proteins of appendage-bearing vertebrates. The profile of Hoxc9 expression inversely correlates with LMC position in land vertebrates and likely accounts for the absence of LMC neurons in limbless species such as snakes. Thus, modulation of both Hoxc9 protein function and Hoxc9 gene expression likely contributed to evolutionary transitions between undulatory and ambulatory motor circuit connectivity programs.

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PMID:
24746670
PMCID:
PMC4024207
DOI:
10.1016/j.devcel.2014.03.008
[Indexed for MEDLINE]
Free PMC Article
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