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eNeuro. 2015 Dec 26;2(6). pii: ENEURO.0096-15.2015. doi: 10.1523/ENEURO.0096-15.2015. eCollection 2015 Nov-Dec.

Loss of Projections, Functional Compensation, and Residual Deficits in the Mammalian Vestibulospinal System of Hoxb1-Deficient Mice.

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Institute of Biology Valrose, UMR 7277, University of Nice Sophia Antipolis, 06108 Nice, France; Institute of Biology Valrose, INSERM, U1091, 06108 Nice, France; Institute of Biology Valrose, CNRS, UMR 7277, 06108 Nice, France.
Division of Physiology, Department of Molecular Medicine, University of Oslo, 0317 Oslo, Norway; Norwegian Center for Stem Cell Research, Oslo University Hospital, 0317 Oslo, Norway.
Institut Génétique Biologie Moléculaire Cellulaire, CNRS UMR 7104, INSERM U 964 , 67404 Illkirch Cedex, Strasbourg, France.


The genetic mechanisms underlying the developmental and functional specification of brainstem projection neurons are poorly understood. Here, we use transgenic mouse tools to investigate the role of the gene Hoxb1 in the developmental patterning of vestibular projection neurons, with particular focus on the lateral vestibulospinal tract (LVST). The LVST is the principal pathway that conveys vestibular information to limb-related spinal motor circuits and arose early during vertebrate evolution. We show that the segmental hindbrain expression domain uniquely defined by the rhombomere 4 (r4) Hoxb1 enhancer is the origin of essentially all LVST neurons, but also gives rise to subpopulations of contralateral medial vestibulospinal tract (cMVST) neurons, vestibulo-ocular neurons, and reticulospinal (RS) neurons. In newborn mice homozygous for a Hoxb1-null mutation, the r4-derived LVST and cMVST subpopulations fail to form and the r4-derived RS neurons are depleted. Several general motor skills appear unimpaired, but hindlimb vestibulospinal reflexes, which are mediated by the LVST, are greatly reduced. This functional deficit recovers, however, during the second postnatal week, indicating a substantial compensation for the missing LVST. Despite the compensatory plasticity in balance, adult Hoxb1-null mice exhibit other behavioral deficits that manifest particularly in proprioception and interlimb coordination during locomotor tasks. Our results provide a comprehensive account of the developmental role of Hoxb1 in patterning the vestibular system and evidence for a remarkable developmental plasticity in the descending control of reflex limb movements. They also suggest an involvement of the lateral vestibulospinal tract in proprioception and in ensuring limb alternation generated by locomotor circuitry.


Hox genes; brain patterning; functional compensation; reticulospinal; vestibulo-ocular; vestibulospinal

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