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

Di Bonito M, Boulland JL, Krezel W, Setti E, Studer M, Glover JC - eNeuro (2015)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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.

ABSTRACT
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- 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- 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.

No MeSH data available.


Related in: MedlinePlus

Summary of segmental origins of vestibular projection neurons, vestibular efferent neurons, and reticulospinal neurons in the wild-type mice (top), and of the phenotype of the same neuron populations in the Hoxb1- mutant mice (bottom).
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Figure 9: Summary of segmental origins of vestibular projection neurons, vestibular efferent neurons, and reticulospinal neurons in the wild-type mice (top), and of the phenotype of the same neuron populations in the Hoxb1- mutant mice (bottom).

Mentions: This places the contribution of r4 to the patterning of vestibular projection neurons into relief. Rhombomere 4 lies about midway along the rostrocaudal extent of the vestibular nuclear complex and represents in several respects a key domain in patterning vestibular projection neurons. It gives rise to the principal vestibulospinal neuron group, the LVST, but to few vestibulo-ocular projection neurons. The other vestibulospinal neuron groups, coursing in the MVST, derive predominantly from the more caudal r5 and r6, although a portion of the cMVST group derives from r4. Thus, within the context of vestibular projection neurons, r4 is primarily related to vestibulospinal specification, whereas vestibulo-ocular projection neurons derive predominantly from more rostral and more caudal rhombomeres (Fig. 9).


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

Di Bonito M, Boulland JL, Krezel W, Setti E, Studer M, Glover JC - eNeuro (2015)

Summary of segmental origins of vestibular projection neurons, vestibular efferent neurons, and reticulospinal neurons in the wild-type mice (top), and of the phenotype of the same neuron populations in the Hoxb1- mutant mice (bottom).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697082&req=5

Figure 9: Summary of segmental origins of vestibular projection neurons, vestibular efferent neurons, and reticulospinal neurons in the wild-type mice (top), and of the phenotype of the same neuron populations in the Hoxb1- mutant mice (bottom).
Mentions: This places the contribution of r4 to the patterning of vestibular projection neurons into relief. Rhombomere 4 lies about midway along the rostrocaudal extent of the vestibular nuclear complex and represents in several respects a key domain in patterning vestibular projection neurons. It gives rise to the principal vestibulospinal neuron group, the LVST, but to few vestibulo-ocular projection neurons. The other vestibulospinal neuron groups, coursing in the MVST, derive predominantly from the more caudal r5 and r6, although a portion of the cMVST group derives from r4. Thus, within the context of vestibular projection neurons, r4 is primarily related to vestibulospinal specification, whereas vestibulo-ocular projection neurons derive predominantly from more rostral and more caudal rhombomeres (Fig. 9).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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.

ABSTRACT
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- 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- 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.

No MeSH data available.


Related in: MedlinePlus