TY - JOUR T1 - Loss of projections, functional compensation and residual deficits in the mammalian vestibulospinal system of <em>Hoxb1</em>-deficient mice JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0096-15.2015 SP - ENEURO.0096-15.2015 AU - Maria Di Bonito AU - Jean-Luc Boulland AU - Wojciech Krezel AU - Eya Setti AU - Michèle Studer AU - Joel C. Glover Y1 - 2015/11/24 UR - http://www.eneuro.org/content/early/2015/11/23/ENEURO.0096-15.2015.abstract N2 - 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.Significance Statement: The mammalian motor system is constructed from neuron groups that acquire specific functional identities in part through the action of patterning genes such as those in the Hox gene family. Here, we assess the role of the Hoxb1 gene in the development of the murine vestibular system. Hoxb1 function is required to generate specific groups of vestibular neurons, in particular neurons that give rise to the lateral vestibulospinal tract (LVST). The lack of the LVST resulting from the absence of Hoxb1 function leads to an initial deficit in vestibulospinal reflexes, but these recover over the course of several days, indicating a pronounced functional compensation. Subtle behavioral deficits are maintained into adulthood, suggesting additional roles for the LVST in motor control, most notably in proprioception and interlimb coordination during locomotion. ER -